Review
. 2014 Jan; 11(2):91-9.
doi: 10.1038/nrclinonc.2013.245.

Mitigating the toxic effects of anticancer immunotherapy

Tara C Gangadhar 1 Robert H Vonderheide 1 
Affiliations
  • PMID: 24445516
  •     67 References
  •     91 citations

Abstract

Advances in our understanding of the regulatory mechanisms of the immune system have led to the development of novel approaches for cancer therapy, including inhibition of immune checkpoints with anti-CTLA-4 and anti-PD-1 antibodies. An increasing number of immunomodulatory treatments are under investigation, and are beginning to show promise in clinical trials. As more-effective therapies become available based on modulation of the immune system in order to trigger or enhance antitumour immune responses, clinicians will need to become familiar with recognizing and controlling the adverse effects arising from immune therapy. This Review describes the toxicity profiles for various anticancer therapies based on the use of agents that block immune checkpoints, immunostimulatory agents, and adoptive T-cell therapy (that is, infusion of modified autologous T cells). The management of patients receiving these treatments presents unique challenges for clinicians. Nevertheless, many of the adverse effects associated with these treatments are reversible and can be managed with supportive care either with or without cessation of therapy. This final point is extremely important given the continued development of new cancer immunotherapies, and the importance of safe and effective use of existing effective FDA-approved agents.

Clinical experiences with anti-CD137 and anti-PD1 therapeutic antibodies.
Paolo A Ascierto, Ester Simeone, +2 authors, Ignacio Melero.
Semin Oncol, 2010 Nov 16; 37(5). PMID: 21074066
Highly Cited. Review.
CD20-specific adoptive immunotherapy for lymphoma using a chimeric antigen receptor with both CD28 and 4-1BB domains: pilot clinical trial results.
Brian G Till, Michael C Jensen, +12 authors, Oliver W Press.
Blood, 2012 Feb 07; 119(17). PMID: 22308288    Free PMC article.
Highly Cited.
Efficacy and safety of retreatment with ipilimumab in patients with pretreated advanced melanoma who progressed after initially achieving disease control.
Caroline Robert, Dirk Schadendorf, +3 authors, MDX010-20 investigators.
Clin Cancer Res, 2013 Feb 28; 19(8). PMID: 23444228
Interleukin-2 and lymphokine-activated killer cell therapy of solid tumors: analysis of toxicity and management guidelines.
K A Margolin, A A Rayner, +7 authors, M Roper.
J Clin Oncol, 1989 Apr 01; 7(4). PMID: 2647914
Nivolumab plus ipilimumab in advanced melanoma.
Jedd D Wolchok, Harriet Kluger, +21 authors, Mario Sznol.
N Engl J Med, 2013 Jun 04; 369(2). PMID: 23724867    Free PMC article.
Highly Cited.
Ipilimumab plus dacarbazine for previously untreated metastatic melanoma.
Caroline Robert, Luc Thomas, +21 authors, Jedd D Wolchok.
N Engl J Med, 2011 Jun 07; 364(26). PMID: 21639810
Highly Cited.
Interferon alpha adjuvant therapy in patients with high-risk melanoma: a systematic review and meta-analysis.
Simone Mocellin, Sandro Pasquali, Carlo R Rossi, Donato Nitti.
J Natl Cancer Inst, 2010 Feb 25; 102(7). PMID: 20179267
Highly Cited. Systematic Review.
High-dose recombinant interleukin 2 therapy for patients with metastatic melanoma: analysis of 270 patients treated between 1985 and 1993.
M B Atkins, M T Lotze, +10 authors, S A Rosenberg.
J Clin Oncol, 1999 Nov 24; 17(7). PMID: 10561265
Highly Cited. Review.
Cytokine storm in a phase 1 trial of the anti-CD28 monoclonal antibody TGN1412.
Ganesh Suntharalingam, Meghan R Perry, +4 authors, Nicki Panoskaltsis.
N Engl J Med, 2006 Aug 16; 355(10). PMID: 16908486
Highly Cited.
Coregulation of CD8+ T cell exhaustion by multiple inhibitory receptors during chronic viral infection.
Shawn D Blackburn, Haina Shin, +7 authors, E John Wherry.
Nat Immunol, 2008 Dec 02; 10(1). PMID: 19043418    Free PMC article.
Highly Cited.
CD40 agonists alter tumor stroma and show efficacy against pancreatic carcinoma in mice and humans.
Gregory L Beatty, Elena G Chiorean, +10 authors, Robert H Vonderheide.
Science, 2011 Mar 26; 331(6024). PMID: 21436454    Free PMC article.
Highly Cited.
Endocrine side effects induced by immune checkpoint inhibitors.
Salvatore Maria Corsello, Agnese Barnabei, +3 authors, Francesco Torino.
J Clin Endocrinol Metab, 2013 Mar 09; 98(4). PMID: 23471977
Highly Cited. Review.
Chimeric antigen receptor-modified T cells in chronic lymphoid leukemia.
David L Porter, Bruce L Levine, +2 authors, Carl H June.
N Engl J Med, 2011 Aug 13; 365(8). PMID: 21830940    Free PMC article.
Highly Cited.
Hepatotoxicity with combination of vemurafenib and ipilimumab.
Antoni Ribas, F Stephen Hodi, +2 authors, Jedd Wolchok.
N Engl J Med, 2013 Apr 05; 368(14). PMID: 23550685
Highly Cited.
Phase III randomized clinical trial comparing tremelimumab with standard-of-care chemotherapy in patients with advanced melanoma.
Antoni Ribas, Richard Kefford, +21 authors, Axel Hauschild.
J Clin Oncol, 2013 Jan 09; 31(5). PMID: 23295794    Free PMC article.
Highly Cited.
Safety and activity of anti-PD-L1 antibody in patients with advanced cancer.
Julie R Brahmer, Scott S Tykodi, +23 authors, Jon M Wigginton.
N Engl J Med, 2012 Jun 05; 366(26). PMID: 22658128    Free PMC article.
Highly Cited.
Enterocolitis in patients with cancer after antibody blockade of cytotoxic T-lymphocyte-associated antigen 4.
Kimberly E Beck, Joseph A Blansfield, +12 authors, James C Yang.
J Clin Oncol, 2006 May 20; 24(15). PMID: 16710025    Free PMC article.
Highly Cited.
Identification of a Titin-derived HLA-A1-presented peptide as a cross-reactive target for engineered MAGE A3-directed T cells.
Brian J Cameron, Andrew B Gerry, +27 authors, Bent K Jakobsen.
Sci Transl Med, 2013 Aug 09; 5(197). PMID: 23926201    Free PMC article.
Highly Cited.
Effects of single-dose interleukin-12 exposure on interleukin-12-associated toxicity and interferon-gamma production.
J P Leonard, M L Sherman, +7 authors, J L Ryan.
Blood, 1997 Nov 05; 90(7). PMID: 9326219
Highly Cited.
Selective BRAF inhibitors induce marked T-cell infiltration into human metastatic melanoma.
James S Wilmott, Georgina V Long, +6 authors, Richard A Scolyer.
Clin Cancer Res, 2011 Dec 14; 18(5). PMID: 22156613
Highly Cited.
Improved survival with ipilimumab in patients with metastatic melanoma.
F Stephen Hodi, Steven J O'Day, +26 authors, Walter J Urba.
N Engl J Med, 2010 Jun 08; 363(8). PMID: 20525992    Free PMC article.
Highly Cited.
Immunostimulatory monoclonal antibodies for cancer therapy.
Ignacio Melero, Sandra Hervas-Stubbs, +2 authors, Lieping Chen.
Nat Rev Cancer, 2007 Jan 26; 7(2). PMID: 17251916
Highly Cited. Review.
Phase I study of the CD40 agonist antibody CP-870,893 combined with carboplatin and paclitaxel in patients with advanced solid tumors.
Robert H Vonderheide, Jennifer M Burg, +5 authors, Omid Hamid.
Oncoimmunology, 2013 Mar 14; 2(1). PMID: 23483678    Free PMC article.
The mechanism of anti-CTLA-4 activity and the negative regulation of T-cell activation.
Jedd D Wolchok, Yvonne Saenger.
Oncologist, 2008 Nov 15; 13 Suppl 4. PMID: 19001145
Review.
Antitumor activity in melanoma and anti-self responses in a phase I trial with the anti-cytotoxic T lymphocyte-associated antigen 4 monoclonal antibody CP-675,206.
Antoni Ribas, Luis H Camacho, +10 authors, Jesus Gomez-Navarro.
J Clin Oncol, 2005 Oct 06; 23(35). PMID: 16204013
Highly Cited.
T cells with chimeric antigen receptors have potent antitumor effects and can establish memory in patients with advanced leukemia.
Michael Kalos, Bruce L Levine, +4 authors, Carl H June.
Sci Transl Med, 2011 Aug 13; 3(95). PMID: 21832238    Free PMC article.
Highly Cited.
Cytotoxic T-lymphocyte-associated antigen-4 blockage can induce autoimmune hypophysitis in patients with metastatic melanoma and renal cancer.
Joseph A Blansfield, Kimberly E Beck, +9 authors, Richard M Sherry.
J Immunother, 2005 Oct 15; 28(6). PMID: 16224277    Free PMC article.
Thyroid dysfunction from antineoplastic agents.
Ole-Petter Riksfjord Hamnvik, P Reed Larsen, Ellen Marqusee.
J Natl Cancer Inst, 2011 Oct 20; 103(21). PMID: 22010182    Free PMC article.
Review.
Co-stimulation through 4-1BB/CD137 improves the expansion and function of CD8(+) melanoma tumor-infiltrating lymphocytes for adoptive T-cell therapy.
Jessica Ann Chacon, Richard C Wu, +6 authors, Laszlo Radvanyi.
PLoS One, 2013 Apr 06; 8(4). PMID: 23560068    Free PMC article.
Adjuvant therapy with pegylated interferon alfa-2b versus observation alone in resected stage III melanoma: final results of EORTC 18991, a randomised phase III trial.
Alexander Mm Eggermont, Stefan Suciu, +14 authors, EORTC Melanoma Group.
Lancet, 2008 Jul 16; 372(9633). PMID: 18620949
Highly Cited.
Safety, activity, and immune correlates of anti-PD-1 antibody in cancer.
Suzanne L Topalian, F Stephen Hodi, +27 authors, Mario Sznol.
N Engl J Med, 2012 Jun 05; 366(26). PMID: 22658127    Free PMC article.
Highly Cited.
CD19-targeted T cells rapidly induce molecular remissions in adults with chemotherapy-refractory acute lymphoblastic leukemia.
Renier J Brentjens, Marco L Davila, +22 authors, Michel Sadelain.
Sci Transl Med, 2013 Mar 22; 5(177). PMID: 23515080    Free PMC article.
Highly Cited.
The CD40 agonist antibody CP-870,893 enhances dendritic cell and B-cell activity and promotes anti-tumor efficacy in SCID-hu mice.
Ronald P Gladue, Timothy Paradis, +8 authors, Vahe Bedian.
Cancer Immunol Immunother, 2011 Apr 12; 60(7). PMID: 21479995
A randomized, double-blind, placebo-controlled, phase II study comparing the tolerability and efficacy of ipilimumab administered with or without prophylactic budesonide in patients with unresectable stage III or IV melanoma.
Jeffrey Weber, John A Thompson, +9 authors, Steven J O'Day.
Clin Cancer Res, 2009 Aug 13; 15(17). PMID: 19671877
Highly Cited.
Case report of a serious adverse event following the administration of T cells transduced with a chimeric antigen receptor recognizing ERBB2.
Richard A Morgan, James C Yang, +3 authors, Steven A Rosenberg.
Mol Ther, 2010 Feb 25; 18(4). PMID: 20179677    Free PMC article.
Highly Cited.
T-cell receptor affinity and avidity defines antitumor response and autoimmunity in T-cell immunotherapy.
Shi Zhong, Karolina Malecek, +12 authors, Michelle Krogsgaard.
Proc Natl Acad Sci U S A, 2013 Apr 12; 110(17). PMID: 23576742    Free PMC article.
Highly Cited.
Cancer regression and autoimmunity induced by cytotoxic T lymphocyte-associated antigen 4 blockade in patients with metastatic melanoma.
Giao Q Phan, James C Yang, +14 authors, Steven A Rosenberg.
Proc Natl Acad Sci U S A, 2003 Jun 27; 100(14). PMID: 12826605    Free PMC article.
Highly Cited.
Cytotoxic T lymphocyte-associated antigen 4 blockade in patients with metastatic melanoma: a new cause of uveitis.
Michael R Robinson, Chi-Chao Chan, +5 authors, Steven A Rosenberg.
J Immunother, 2004 Nov 10; 27(6). PMID: 15534492
Autoimmunity correlates with tumor regression in patients with metastatic melanoma treated with anti-cytotoxic T-lymphocyte antigen-4.
Peter Attia, Giao Q Phan, +14 authors, Steven A Rosenberg.
J Clin Oncol, 2005 Aug 10; 23(25). PMID: 16087944    Free PMC article.
Highly Cited.
Anti-CTLA-4 antibody-induced Guillain-Barré syndrome in a melanoma patient.
S Wilgenhof, B Neyns.
Ann Oncol, 2011 Mar 02; 22(4). PMID: 21357649
The emerging toxicity profiles of anti-CTLA-4 antibodies across clinical indications.
Anna Maria Di Giacomo, Maurizio Biagioli, Michele Maio.
Semin Oncol, 2010 Nov 16; 37(5). PMID: 21074065
Review.
Antitumor activity and long-term fate of chimeric antigen receptor-positive T cells in patients with neuroblastoma.
Chrystal U Louis, Barbara Savoldo, +14 authors, Malcolm K Brenner.
Blood, 2011 Oct 11; 118(23). PMID: 21984804    Free PMC article.
Highly Cited.
Clinical activity and immune modulation in cancer patients treated with CP-870,893, a novel CD40 agonist monoclonal antibody.
Robert H Vonderheide, Keith T Flaherty, +12 authors, Scott J Antonia.
J Clin Oncol, 2007 Mar 01; 25(7). PMID: 17327609
Highly Cited.
Agonistic CD40 antibodies and cancer therapy.
Robert H Vonderheide, Martin J Glennie.
Clin Cancer Res, 2013 Mar 06; 19(5). PMID: 23460534    Free PMC article.
Highly Cited.
Strength of PD-1 signaling differentially affects T-cell effector functions.
Fang Wei, Shi Zhong, +6 authors, James L Riley.
Proc Natl Acad Sci U S A, 2013 Apr 24; 110(27). PMID: 23610399    Free PMC article.
Highly Cited.
Ipilimumab efficacy and safety in patients with advanced melanoma: a retrospective analysis of HLA subtype from four trials.
Jedd D Wolchok, Jeffrey S Weber, +9 authors, Steven J O'Day.
Cancer Immun, 2010 Oct 21; 10. PMID: 20957980    Free PMC article.
Mechanisms and management of toxicities associated with high-dose interferon alfa-2b therapy.
John M Kirkwood, Catherine Bender, +5 authors, Lori Stover.
J Clin Oncol, 2002 Aug 31; 20(17). PMID: 12202672
Review.
Ipilimumab-associated colitis: CT findings.
Kyung Won Kim, Nikhil H Ramaiya, +4 authors, Nageatte Ibrahim.
AJR Am J Roentgenol, 2013 May 31; 200(5). PMID: 23718569
CTLA-4 and PD-1 receptors inhibit T-cell activation by distinct mechanisms.
Richard V Parry, Jens M Chemnitz, +6 authors, James L Riley.
Mol Cell Biol, 2005 Oct 18; 25(21). PMID: 16227604    Free PMC article.
Highly Cited.
Adoptive T cell transfer for cancer immunotherapy in the era of synthetic biology.
Michael Kalos, Carl H June.
Immunity, 2013 Jul 31; 39(1). PMID: 23890063    Free PMC article.
Highly Cited. Review.
B-cell depletion and remissions of malignancy along with cytokine-associated toxicity in a clinical trial of anti-CD19 chimeric-antigen-receptor-transduced T cells.
James N Kochenderfer, Mark E Dudley, +15 authors, Steven A Rosenberg.
Blood, 2011 Dec 14; 119(12). PMID: 22160384    Free PMC article.
Highly Cited.
Durable complete responses in heavily pretreated patients with metastatic melanoma using T-cell transfer immunotherapy.
Steven A Rosenberg, James C Yang, +12 authors, Mark E Dudley.
Clin Cancer Res, 2011 Apr 19; 17(13). PMID: 21498393    Free PMC article.
Highly Cited.
Treatment of chronic lymphocytic leukemia with genetically targeted autologous T cells: case report of an unforeseen adverse event in a phase I clinical trial.
Renier Brentjens, Raymond Yeh, +2 authors, Michel Sadelain.
Mol Ther, 2010 Apr 02; 18(4). PMID: 20357779    Free PMC article.
Highly Cited.
A pooled analysis of eastern cooperative oncology group and intergroup trials of adjuvant high-dose interferon for melanoma.
John M Kirkwood, Judith Manola, +4 authors, Eastern Cooperative Oncology Group.
Clin Cancer Res, 2004 Mar 12; 10(5). PMID: 15014018
Highly Cited.
The blockade of immune checkpoints in cancer immunotherapy.
Drew M Pardoll.
Nat Rev Cancer, 2012 Mar 23; 12(4). PMID: 22437870    Free PMC article.
Highly Cited. Review.
A translational bridge to cancer immunotherapy: exploiting costimulation and target antigens for active and passive T cell immunotherapy.
Robert H Vonderheide, Carl H June.
Immunol Res, 2003 Jul 15; 27(2-3). PMID: 12857980
Review.
Management of immune-related adverse events and kinetics of response with ipilimumab.
Jeffrey S Weber, Katharina C Kähler, Axel Hauschild.
J Clin Oncol, 2012 May 23; 30(21). PMID: 22614989
Highly Cited. Review.
Cancer regression and neurological toxicity following anti-MAGE-A3 TCR gene therapy.
Richard A Morgan, Nachimuthu Chinnasamy, +28 authors, Steven A Rosenberg.
J Immunother, 2013 Feb 05; 36(2). PMID: 23377668    Free PMC article.
Highly Cited.
Lymphoproliferative disorder in CTLA-4 knockout mice is characterized by CD28-regulated activation of Th2 responses.
R Khattri, J A Auger, +2 authors, J A Bluestone.
J Immunol, 1999 May 07; 162(10). PMID: 10229811
Cardiovascular toxicity and titin cross-reactivity of affinity-enhanced T cells in myeloma and melanoma.
Gerald P Linette, Edward A Stadtmauer, +20 authors, Carl H June.
Blood, 2013 Jun 19; 122(6). PMID: 23770775    Free PMC article.
Highly Cited.
Chimeric antigen receptor-modified T cells for acute lymphoid leukemia.
Stephan A Grupp, Michael Kalos, +10 authors, Carl H June.
N Engl J Med, 2013 Mar 27; 368(16). PMID: 23527958    Free PMC article.
Highly Cited.
The road to recovery: translating PD-1 biology into clinical benefit.
James L Riley, Carl H June.
Trends Immunol, 2006 Dec 26; 28(2). PMID: 17188572
Combination checkpoint blockade--taking melanoma immunotherapy to the next level.
James L Riley.
N Engl J Med, 2013 Jun 04; 369(2). PMID: 23724866
Tumor immunotherapy directed at PD-1.
Antoni Ribas.
N Engl J Med, 2012 Jun 05; 366(26). PMID: 22658126
Highly Cited.
Safety and tumor responses with lambrolizumab (anti-PD-1) in melanoma.
Omid Hamid, Caroline Robert, +23 authors, Antoni Ribas.
N Engl J Med, 2013 Jun 04; 369(2). PMID: 23724846    Free PMC article.
Highly Cited.
Prognostic factors related to clinical response in patients with metastatic melanoma treated by CTL-associated antigen-4 blockade.
Stephanie G Downey, Jacob A Klapper, +12 authors, Steven A Rosenberg.
Clin Cancer Res, 2007 Nov 06; 13(22 Pt 1). PMID: 17982122    Free PMC article.
Highly Cited.
CTLA-4 blockade with monoclonal antibodies in patients with metastatic cancer: surgical issues.
Giao Q Phan, Jeffrey S Weber, Vernon K Sondak.
Ann Surg Oncol, 2008 Aug 22; 15(11). PMID: 18716842
Review.
Immune modulation for cancer therapy.
J Naidoo, D B Page, J D Wolchok.
Br J Cancer, 2014 Sep 12; 111(12). PMID: 25211661    Free PMC article.
Review.
Immune activation and a 9-year ongoing complete remission following CD40 antibody therapy and metastasectomy in a patient with metastatic melanoma.
David L Bajor, Xiaowei Xu, +8 authors, Robert H Vonderheide.
Cancer Immunol Res, 2014 Sep 26; 2(11). PMID: 25252722    Free PMC article.
Targeting CD8+ T-cell tolerance for cancer immunotherapy.
Stephanie R Jackson, Jinyun Yuan, Ryan M Teague.
Immunotherapy, 2014 Oct 08; 6(7). PMID: 25290416    Free PMC article.
Review.
PD-1/PD-L1 blockade together with vaccine therapy facilitates effector T-cell infiltration into pancreatic tumors.
Kevin C Soares, Agnieszka A Rucki, +15 authors, Lei Zheng.
J Immunother, 2014 Nov 22; 38(1). PMID: 25415283    Free PMC article.
Highly Cited.
CIMT 2014: Next waves in cancer immunotherapy--report on the 12th annual meeting of the Association for Cancer Immunotherapy: May 6–8 2014, Mainz, Germany.
Mustafa Diken, Sebastian Boegel, +6 authors, Sebastian Kreiter.
Hum Vaccin Immunother, 2014 Dec 09; 10(10). PMID: 25483671    Free PMC article.
Phosphatase of regenerating liver in hematopoietic stem cells and hematological malignancies.
Michihiro Kobayashi, Sisi Chen, +3 authors, Yan Liu.
Cell Cycle, 2014 Dec 09; 13(18). PMID: 25486470    Free PMC article.
Review.
Improved mouse models to assess tumour immunity and irAEs after combination cancer immunotherapies.
Jing Liu, Stephen J Blake, Mark J Smyth, Michele Wl Teng.
Clin Transl Immunology, 2014 Dec 17; 3(8). PMID: 25505970    Free PMC article.
Review.
Checkpoint blockade immunotherapy relies on T-bet but not Eomes to induce effector function in tumor-infiltrating CD8+ T cells.
Melissa M Berrien-Elliott, Jinyun Yuan, +4 authors, Ryan M Teague.
Cancer Immunol Res, 2014 Dec 18; 3(2). PMID: 25516478    Free PMC article.
CTLA-4 blockade with ipilimumab: biology, safety, efficacy, and future considerations.
Luis H Camacho.
Cancer Med, 2015 Jan 27; 4(5). PMID: 25619164    Free PMC article.
Review.
Systemic Agonistic Anti-CD40 Treatment of Tumor-Bearing Mice Modulates Hepatic Myeloid-Suppressive Cells and Causes Immune-Mediated Liver Damage.
José Medina-Echeverz, Chi Ma, +5 authors, Tim F Greten.
Cancer Immunol Res, 2015 Feb 01; 3(5). PMID: 25637366    Free PMC article.
Obesity and cancer immunotherapy toxicity.
Annie Mirsoian, William J Murphy.
Immunotherapy, 2015 Apr 29; 7(4). PMID: 25917623    Free PMC article.
PD-1/PD-L1 inhibitors.
Joel Sunshine, Janis M Taube.
Curr Opin Pharmacol, 2015 Jun 07; 23. PMID: 26047524    Free PMC article.
Highly Cited. Review.
The pharmacology of second-generation chimeric antigen receptors.
Sjoukje J C van der Stegen, Mohamad Hamieh, Michel Sadelain.
Nat Rev Drug Discov, 2015 Jul 02; 14(7). PMID: 26129802    Free PMC article.
Highly Cited. Review.
Ipilimumab-associated colitis or refractory Clostridium difficile infection?
Arjun Gupta, Sahil Khanna.
BMJ Case Rep, 2015 Jul 15; 2015. PMID: 26153295    Free PMC article.
Evolving synergistic combinations of targeted immunotherapies to combat cancer.
Ignacio Melero, David M Berman, +3 authors, John Haanen.
Nat Rev Cancer, 2015 Jul 25; 15(8). PMID: 26205340
Highly Cited. Review.
Pembrolizumab.
Leila Khoja, Marcus O Butler, +2 authors, Anthony M Joshua.
J Immunother Cancer, 2015 Aug 20; 3. PMID: 26288737    Free PMC article.
Review.
The PTEN pathway in Tregs is a critical driver of the suppressive tumor microenvironment.
Madhav D Sharma, Rahul Shinde, +12 authors, David H Munn.
Sci Adv, 2015 Nov 26; 1(10). PMID: 26601142    Free PMC article.
Highly Cited.
Current progress in immunotherapy for pancreatic cancer.
Kelly Foley, Victoria Kim, Elizabeth Jaffee, Lei Zheng.
Cancer Lett, 2016 Jan 03; 381(1). PMID: 26723878    Free PMC article.
Highly Cited. Review.
Nivolumab causing painless thyroiditis in a patient with adenocarcinoma of the lung.
Isha Verma, Anar Modi, Hemantkumar Tripathi, Abhinav Agrawal.
BMJ Case Rep, 2016 Jan 07; 2016. PMID: 26733436    Free PMC article.
Viro-immune therapy: A new strategy for treatment of pancreatic cancer.
Andrea Marie Ibrahim, Yao-He Wang.
World J Gastroenterol, 2016 Jan 27; 22(2). PMID: 26811622    Free PMC article.
Review.
Ipilimumab (Anti-Ctla-4 Mab) in the treatment of metastatic melanoma: Effectiveness and toxicity management.
Paola Savoia, Chiara Astrua, Paolo Fava.
Hum Vaccin Immunother, 2016 Feb 19; 12(5). PMID: 26889818    Free PMC article.
Review.
The Role of Neoantigens in Naturally Occurring and Therapeutically Induced Immune Responses to Cancer.
Jeffrey P Ward, Matthew M Gubin, Robert D Schreiber.
Adv Immunol, 2016 Mar 01; 130. PMID: 26922999    Free PMC article.
Highly Cited. Review.
Immunotherapy and Novel Combinations in Oncology: Current Landscape, Challenges, and Opportunities.
K M Morrissey, T M Yuraszeck, +2 authors, S Kasichayanula.
Clin Transl Sci, 2016 Mar 01; 9(2). PMID: 26924066    Free PMC article.
Highly Cited. Review.
MRP1-CD28 bi-specific oligonucleotide aptamers: target costimulation to drug-resistant melanoma cancer stem cells.
Mario Martínez Soldevilla, Helena Villanueva, +5 authors, Fernando Pastor.
Oncotarget, 2016 Mar 19; 7(17). PMID: 26992239    Free PMC article.
Reporter nanoparticle that monitors its anticancer efficacy in real time.
Ashish Kulkarni, Poornima Rao, +7 authors, Shiladitya Sengupta.
Proc Natl Acad Sci U S A, 2016 Apr 02; 113(15). PMID: 27036008    Free PMC article.
Characterisation and management of dermatologic adverse events to agents targeting the PD-1 receptor.
V R Belum, B Benhuri, +8 authors, M E Lacouture.
Eur J Cancer, 2016 Apr 05; 60. PMID: 27043866    Free PMC article.
Highly Cited. Systematic Review.
Adapting Cancer Immunotherapy Models for the Real World.
Lauryn E Klevorn, Ryan M Teague.
Trends Immunol, 2016 Apr 24; 37(6). PMID: 27105824    Free PMC article.
Review.
Recent advances in the management of Hodgkin lymphoma.
Jose C Villasboas, Stephen M Ansell.
F1000Res, 2016 May 10; 5. PMID: 27158471    Free PMC article.
Review.
Metastatic melanoma and immunotherapy.
Benjamin Herzberg, David E Fisher.
Clin Immunol, 2016 Jul 20; 172. PMID: 27430520    Free PMC article.
Review.
Looking beyond the cancer cell for effective drug combinations.
Jonathan R Dry, Mi Yang, Julio Saez-Rodriguez.
Genome Med, 2016 Nov 27; 8(1). PMID: 27887656    Free PMC article.
Rapid and partial remission of primary lesion but complicated by secondary fibrosis after treatment with nivolumab in a lung squamous carcinoma.
Ling Ding, Yehan Zhu, Cheng Chen.
Ther Adv Respir Dis, 2016 Dec 03; 11(2). PMID: 27903791    Free PMC article.
Immuno-Oncology: The Third Paradigm in Early Drug Development.
Juan Martin-Liberal, Cinta Hierro, Maria Ochoa de Olza, Jordi Rodon.
Target Oncol, 2016 Dec 21; 12(2). PMID: 27995439
Impact of CTLA-4 blockade in conjunction with metronomic chemotherapy on preclinical breast cancer growth.
Karla Parra, Paloma Valenzuela, +10 authors, Giulio Francia.
Br J Cancer, 2017 Jan 06; 116(3). PMID: 28056464    Free PMC article.
Current Diagnosis and Management of Immune Related Adverse Events (irAEs) Induced by Immune Checkpoint Inhibitor Therapy.
Vivek Kumar, Neha Chaudhary, +3 authors, Abhinav B Chandra.
Front Pharmacol, 2017 Feb 24; 8. PMID: 28228726    Free PMC article.
Highly Cited. Review.
Anti-PD-L1 atezolizumab-Induced Autoimmune Diabetes: a Case Report and Review of the Literature.
Laura Hickmott, Hugo De La Peña, +4 authors, Avinash Gupta.
Target Oncol, 2017 Mar 04; 12(2). PMID: 28255845
Review.
Immunotherapy for Breast Cancer: What Are We Missing?
Robert H Vonderheide, Susan M Domchek, Amy S Clark.
Clin Cancer Res, 2017 Jun 03; 23(11). PMID: 28572258    Free PMC article.
Highly Cited.
Post-nano strategies for drug delivery: Multistage porous silicon microvectors.
Alessandro Venuta, Joy Wolfram, Haifa Shen, Mauro Ferrari.
J Mater Chem B, 2017 Jul 04; 5(2). PMID: 28670454    Free PMC article.
Optimizing tumor immune response through combination of radiation and immunotherapy.
Alissar El Chediak, Ali Shamseddine, +3 authors, Youssef H Zeidan.
Med Oncol, 2017 Aug 23; 34(9). PMID: 28828581
Review.
Analysis of B7-H4 expression in metastatic pleural adenocarcinoma and therapeutic potential of its antagonists.
Cheng Chen, Qiu-Xia Qu, +3 authors, Jian-An Huang.
BMC Cancer, 2017 Sep 20; 17(1). PMID: 28923053    Free PMC article.
Checkpoint Inhibitors: Applications for Autoimmunity.
Anna S Tocheva, Adam Mor.
Curr Allergy Asthma Rep, 2017 Sep 29; 17(10). PMID: 28956259    Free PMC article.
Review.
Pneumonitis and pneumonitis-related death in cancer patients treated with programmed cell death-1 inhibitors: a systematic review and meta-analysis.
Peng-Fei Cui, Jun-Xun Ma, +3 authors, Yi Hu.
Ther Clin Risk Manag, 2017 Oct 14; 13. PMID: 29026313    Free PMC article.
Radiomics to predict immunotherapy-induced pneumonitis: proof of concept.
Rivka R Colen, Takeo Fujii, +16 authors, Aung Naing.
Invest New Drugs, 2017 Oct 28; 36(4). PMID: 29075985    Free PMC article.
Cardiotoxicity of immune checkpoint inhibitors.
Gilda Varricchi, Maria Rosaria Galdiero, +5 authors, Carlo Gabriele Tocchetti.
ESMO Open, 2017 Nov 07; 2(4). PMID: 29104763    Free PMC article.
Highly Cited. Review.
Biodegradable STING agonist nanoparticles for enhanced cancer immunotherapy.
David R Wilson, Rupashree Sen, +3 authors, Young J Kim.
Nanomedicine, 2017 Nov 12; 14(2). PMID: 29127039    Free PMC article.
Highly Cited.
Emerging biomarkers for the combination of radiotherapy and immune checkpoint blockers.
Claire Lhuillier, Claire Vanpouille-Box, +2 authors, Sandra Demaria.
Semin Cancer Biol, 2017 Dec 21; 52(Pt 2). PMID: 29258856    Free PMC article.
Review.
How Checkpoint Inhibitors Are Changing the Treatment Paradigm in Solid Tumors: What Advanced Practitioners in Oncology Need to Know.
Marianne Davies.
J Adv Pract Oncol, 2016 Jul 01; 7(5). PMID: 29282426    Free PMC article.
Review.
Immune Checkpoints in Leprosy: Immunotherapy As a Feasible Approach to Control Disease Progression.
Hayana Ramos Lima, Thaís Helena Gasparoto, +10 authors, Ana Paula Campanelli.
Front Immunol, 2018 Jan 10; 8. PMID: 29312289    Free PMC article.
Semaphorin 4D in human head and neck cancer tissue and peripheral blood: A dense fibrotic peri-tumoral stromal phenotype.
Roshanak Derakhshandeh, Sonia Sanadhya, +4 authors, Rania H Younis.
Oncotarget, 2018 Mar 16; 9(13). PMID: 29541402    Free PMC article.
Coming of Age for Autotaxin and Lysophosphatidate Signaling: Clinical Applications for Preventing, Detecting and Targeting Tumor-Promoting Inflammation.
Matthew G K Benesch, Iain T K MacIntyre, Todd P W McMullen, David N Brindley.
Cancers (Basel), 2018 Mar 16; 10(3). PMID: 29543710    Free PMC article.
Highly Cited. Review.
Dendritic Cells and Programmed Death-1 Blockade: A Joint Venture to Combat Cancer.
Maarten Versteven, Johan M J Van den Bergh, +4 authors, Eva Lion.
Front Immunol, 2018 Mar 31; 9. PMID: 29599770    Free PMC article.
Highly Cited. Review.
Deciphering mechanisms of brain metastasis in melanoma - the gist of the matter.
Torben Redmer.
Mol Cancer, 2018 Jul 29; 17(1). PMID: 30053879    Free PMC article.
Review.
Management of the cutaneous adverse effects of antimelanoma therapy.
Rose Congwei Liu, Germana Consuegra, Pablo Fernández-Peñas.
Melanoma Manag, 2018 Sep 08; 4(4). PMID: 30190925    Free PMC article.
Review.
Combination with SGT-53 overcomes tumor resistance to a checkpoint inhibitor.
Sang-Soo Kim, Joe B Harford, +2 authors, Esther H Chang.
Oncoimmunology, 2018 Oct 06; 7(10). PMID: 30288347    Free PMC article.
Comparative safety of immune checkpoint inhibitors in cancer: systematic review and network meta-analysis.
Cheng Xu, Yu-Pei Chen, +12 authors, Jun Ma.
BMJ, 2018 Nov 10; 363. PMID: 30409774    Free PMC article.
Highly Cited. Systematic Review.
BRAF and MEK inhibitors differentially affect nivolumab-induced T cell activation by modulating the TCR and AKT signaling pathways.
Peng Yue, Taylor Harper, +6 authors, Gerald M Feldman.
Oncoimmunology, 2018 Dec 14; 8(1). PMID: 30546949    Free PMC article.
Synergistic cancer immunotherapy combines MVA-CD40L induced innate and adaptive immunity with tumor targeting antibodies.
José Medina-Echeverz, Maria Hinterberger, +11 authors, Henning Lauterbach.
Nat Commun, 2019 Nov 07; 10(1). PMID: 31695037    Free PMC article.
Tumor-targeted silencing of the peptide transporter TAP induces potent antitumor immunity.
Greta Garrido, Brett Schrand, +10 authors, Eli Gilboa.
Nat Commun, 2019 Aug 23; 10(1). PMID: 31434881    Free PMC article.
Sorafenib: Experience and Better Manage-ment of Side Effects Improve Overall Survival in Hepatocellular Carcinoma Patients: A Real-Life Retrospective Analysis.
Jean-Luc Raoul, Xavier Adhoute, +4 authors, Marc Bourlière.
Liver Cancer, 2019 Dec 05; 8(6). PMID: 31799203    Free PMC article.
Siglec-15 as an immune suppressor and potential target for normalization cancer immunotherapy.
Jun Wang, Jingwei Sun, +16 authors, Lieping Chen.
Nat Med, 2019 Mar 06; 25(4). PMID: 30833750    Free PMC article.
Highly Cited.
STING modulators: Predictive significance in drug discovery.
Xiangling Cui, Rongyu Zhang, Shan Cen, Jinming Zhou.
Eur J Med Chem, 2019 Aug 17; 182. PMID: 31419779    Free PMC article.
Review.
Combination therapy targeting both innate and adaptive immunity improves survival in a pre-clinical model of ovarian cancer.
Christina A Hartl, Adrian Bertschi, +5 authors, Michael S Goldberg.
J Immunother Cancer, 2019 Aug 01; 7(1). PMID: 31362778    Free PMC article.
From Molecular Mechanisms to Clinical Management of Antineoplastic Drug-Induced Cardiovascular Toxicity: A Translational Overview.
Carlo Gabriele Tocchetti, Christian Cadeddu, +12 authors, Giuseppe Mercuro.
Antioxid Redox Signal, 2017 Apr 12; 30(18). PMID: 28398124    Free PMC article.
Review.
Vaccination against Nonmutated Neoantigens Induced in Recurrent and Future Tumors.
Greta Garrido, Brett Schrand, +12 authors, Eli Gilboa.
Cancer Immunol Res, 2020 Apr 17; 8(7). PMID: 32295785    Free PMC article.
Nanomedicine and macroscale materials in immuno-oncology.
Qingxue Sun, Matthias Barz, +5 authors, Yang Shi.
Chem Soc Rev, 2018 Nov 23; 48(1). PMID: 30465669    Free PMC article.
Review.
The rationale for including immune checkpoint inhibition into multimodal primary treatment concepts of head and neck cancer.
Ingeborg Tinhofer, Volker Budach, Korinna Jöhrens, Ulrich Keilholz.
Cancers Head Neck, 2016 Aug 10; 1. PMID: 31093338    Free PMC article.
Review.
Immunosuppressive checkpoint Siglec-15: a vital new piece of the cancer immunotherapy jigsaw puzzle.
Xiubao Ren.
Cancer Biol Med, 2019 Sep 14; 16(2). PMID: 31516742    Free PMC article.
Enhancing cancer immunotherapy with nanomedicine.
Darrell J Irvine, Eric L Dane.
Nat Rev Immunol, 2020 Feb 02; 20(5). PMID: 32005979    Free PMC article.
Review.
Radiation-Induced Enhancement of Antitumor T-cell Immunity by VEGF-Targeted 4-1BB Costimulation.
Brett Schrand, Bhavna Verma, +8 authors, Adrian Ishkanian.
Cancer Res, 2017 Jan 14; 77(6). PMID: 28082399    Free PMC article.
Immune Checkpoint Inhibitor-Induced Thyroiditis Is Associated with Increased Intrathyroidal T Lymphocyte Subpopulations.
Anupam Kotwal, Michael P Gustafson, +5 authors, Mabel Ryder.
Thyroid, 2020 Apr 24; 30(10). PMID: 32323619    Free PMC article.
Fructose Promotes Cytoprotection in Melanoma Tumors and Resistance to Immunotherapy.
Lindsey M Kuehm, Niloufar Khojandi, +13 authors, Ryan M Teague.
Cancer Immunol Res, 2020 Oct 08; 9(2). PMID: 33023966    Free PMC article.
Healthy cells functionally present TAP-independent SSR1 peptides: implications for selection of clinically relevant antigens.
Antonius A de Waard, Tamara Verkerk, +10 authors, Robbert M Spaapen.
iScience, 2021 Feb 09; 24(2). PMID: 33554062    Free PMC article.
Treatment- and immune-related adverse events of immune checkpoint inhibitors in advanced lung cancer.
Jun Shao, Chengdi Wang, +3 authors, Weimin Li.
Biosci Rep, 2020 Apr 22; 40(5). PMID: 32315071    Free PMC article.
Systematic Review.
Knowledge gap about immune checkpoint inhibitors among rheumatologists and medical students: a survey.
Guilherme Ferreira Maciel da Silva, Joaquim Ivo Vasques Dantas Landim, +4 authors, Francisco Airton Castro Rocha.
Rheumatol Int, 2020 Aug 09; 41(5). PMID: 32767082
A Review of Cancer Immunotherapy Toxicity II: Adoptive Cellular Therapies, Kinase Inhibitors, Monoclonal Antibodies, and Oncolytic Viruses.
Neeraj Chhabra, Joseph Kennedy.
J Med Toxicol, 2021 Apr 07; 18(1). PMID: 33821435    Free PMC article.
Review.
Stoichiometry of multi-specific immune checkpoint RNA Abs for T cell activation and tumor inhibition using ultra-stable RNA nanoparticles.
Dan Shu, Long Zhang, +2 authors, Peixuan Guo.
Mol Ther Nucleic Acids, 2021 Apr 20; 24. PMID: 33868786    Free PMC article.
SQ3370 Activates Cytotoxic Drug via Click Chemistry at Tumor and Elicits Sustained Responses in Injected & Non-injected Lesions.
S Srinivasan, N A Yee, +4 authors, J M Mejia Oneto.
Adv Ther (Weinh), 2021 Apr 20; 4(3). PMID: 33869738    Free PMC article.
Efficacy and side effects of immune checkpoint inhibitors in the treatment of colorectal cancer.
Salomon M Manz, Marco Losa, Ralph Fritsch, Michael Scharl.
Therap Adv Gastroenterol, 2021 May 06; 14. PMID: 33948110    Free PMC article.
Review.
The Cytosolic DNA-Sensing cGAS-STING Pathway in Liver Diseases.
Zhilei Wang, Nian Chen, +5 authors, Zhaofang Bai.
Front Cell Dev Biol, 2021 Aug 14; 9. PMID: 34386500    Free PMC article.
Review.
Adrenaline fuels a cytokine storm during immunotherapy.
Stanley R RIddell.
Nature, 2018 Dec 14; 564(7735). PMID: 30542198
High Granulocyte-Macrophage Colony Stimulating Factor to Interleukin 10 Ratio and Marked Antioxidant Enzyme Activities Predominate in Symptomatic Cattle Naturally Infected with Candidatus Mycoplasma haemobos, Theileria orientalis, Theileria sinensis and Trypanosoma evansi.
Onyinyechukwu Ada Agina, Kim Tho Cheah, +6 authors, Hazilawati Hamzah.
Animals (Basel), 2021 Aug 28; 11(8). PMID: 34438696    Free PMC article.
TNF blockade uncouples toxicity from antitumor efficacy induced with CD40 chemoimmunotherapy.
Meredith L Stone, Jesse Lee, +11 authors, Gregory L Beatty.
JCI Insight, 2021 Jun 09; 6(14). PMID: 34101617    Free PMC article.
Safety profile of poly (ADP-ribose) polymerase (PARP) inhibitors in cancer: a network meta-analysis of randomized controlled trials.
Shengnan Bao, Yuanping Yue, +13 authors, Yongmei Yin.
Ann Transl Med, 2021 Sep 18; 9(15). PMID: 34532366    Free PMC article.
Prolonged survival in patients with hand-foot skin reaction secondary to cooperative sorafenib treatment.
Masanori Ochi, Toshiro Kamoshida, Masahiro Araki, Tadashi Ikegami.
World J Gastroenterol, 2021 Sep 21; 27(32). PMID: 34539142    Free PMC article.
PD-1/PD-L1 Checkpoint Inhibitors in Tumor Immunotherapy.
Jinhua Liu, Zichao Chen, +3 authors, Zhen Zhang.
Front Pharmacol, 2021 Sep 21; 12. PMID: 34539412    Free PMC article.
Review.
PD-L1 Inhibitors as Monotherapy for the First-Line Treatment of Non-Small-Cell Lung Cancer in PD-L1 Positive Patients: A Safety Data Network Meta-Analysis.
María Rosario García Campelo, Edurne Arriola, +8 authors, Delvys Rodríguez-Abreu.
J Clin Med, 2021 Oct 14; 10(19). PMID: 34640601    Free PMC article.
Review.
Immune Checkpoint Inhibitors and the Heart.
Diana Larisa Mocan-Hognogi, Sebastian Trancǎ, +3 authors, Anca Simona Bojan.
Front Cardiovasc Med, 2021 Oct 19; 8. PMID: 34660728    Free PMC article.
Review.
Metabolic Reprogramming in the Tumor Microenvironment With Immunocytes and Immune Checkpoints.
Yaolin Xu, Lijie He, Qiang Fu, Junzhe Hu.
Front Oncol, 2021 Dec 04; 11. PMID: 34858835    Free PMC article.
Review.
A Network Comparison on Safety Profiling of Immune Checkpoint Inhibitors in Advanced Lung Cancer.
Yi-Dan Yan, Jiu-Jie Cui, +4 authors, Hou-Wen Lin.
Front Immunol, 2021 Dec 21; 12. PMID: 34925331    Free PMC article.
Systematic Review.
The cGAS-STING signaling in cardiovascular and metabolic diseases: Future novel target option for pharmacotherapy.
Patrick Kwabena Oduro, Xianxian Zheng, +7 authors, Qilong Wang.
Acta Pharm Sin B, 2022 Feb 08; 12(1). PMID: 35127372    Free PMC article.
Review.
Safety of Immune Checkpoint Inhibitor Resumption after Interruption for Immune-Related Adverse Events, a Narrative Review.
Marion Allouchery, Clément Beuvon, +3 authors, Mickaël Martin.
Cancers (Basel), 2022 Feb 26; 14(4). PMID: 35205703    Free PMC article.
Review.
Enhanced Cancer Therapy Using an Engineered Designer Cytokine Alone and in Combination With an Immune Checkpoint Inhibitor.
Anjan K Pradhan, Praveen Bhoopathi, +9 authors, Paul B Fisher.
Front Oncol, 2022 Apr 12; 12. PMID: 35402258    Free PMC article.