The Great Debate at 'Immunotherapy Bridge', Naples, December 5, 2019

Paolo A Ascierto ¹, Carlo Bifulco ², Jerome Galon ³, Claus Garbe ⁴, Samir N Khleif ⁵, Jennifer McQuade ⁶, Kunle Odunsi ⁷, Hideho Okada ⁸, Chrystal M Paulos ⁹, Sergio A Quezada ¹⁰, Hussein A Tawbi ⁶, John Timmerman ¹¹, Giorgio Trinchieri ¹², Lisa H Butterfield ¹³, Igor Puzanov ¹⁴

Affiliations

¹ Cancer Unit of Melanoma, Cancer Immunotherapy and Development Therapeutics, Istituto Nazionale Tumori IRCCS Fondazione Pascale, Napoli, Italy paolo.ascierto@gmail.com.
² Earle A. Chiles Research Institute, Robert W. Franz Cancer Research Center, Providence Portland Medical Center, Portland, Oregon, USA.
³ Laboratory of Integrative Cancer Immunology, Equipe Labellisée Ligue Contre le Cancer, Centre de Recherche des Cordeliers, INSERM, Paris, Île-de-France, France.
⁴ Center for Dermatooncology, Department of Dermatology, Eberhard Karls University Tübingen, Tubingen, Baden-Württemberg, Germany.
⁵ The Loop Immuno-Oncology Research Laboratory, Lombardi Cancer Center, Georgetown University, Washington, District of Columbia, USA.
⁶ Department of Melanoma Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
⁷ Center for Immunotherapy and Department of Gynaecologic Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, New York, USA.
⁸ Department of Neurological Surgery, Parker Institute for Cancer Immunotherapy, UCSF, San Francisco, California, USA.
⁹ Department of Microbiology and Immunology Hollings Cancer Center, MUSC, Charleston, South Carolina, USA.
¹⁰ Cancer Immunology Unit, Research Department of Haematology, University College London Cancer Institute, London, UK.
¹¹ Santa Monica UCLA Medical Center, University of California Los Angeles, Los Angeles, California, USA.
¹² Laboratory of Integrative Cancer Immunology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
¹³ PICI Research and Development, Parker Institute for Cancer Immunotherapy, UCSF, San Francisco, California, USA.
¹⁴ Early Phase Clinical Trials Program, Developmental Therapeutics Program, Roswell Park Comprehensive Cancer Center, Buffalo, New York, USA.

PMID: 32843491
48 References
1 citations

Abstract

As part of the 2019 Immunotherapy Bridge congress (December 4-5, Naples, Italy), the Great Debate session featured counterpoint views from leading experts on six topical issues in immunotherapy today. These were the use of chimeric antigen receptor T cell therapy in solid tumors, whether the Immunoscore should be more widely used in clinical practice, whether antibody-dependent cellular cytotoxicity is important in the mode of action of anticytotoxic T-lymphocyte-associated protein 4 antibodies, whether the brain is immunologically unique or just another organ, the role of microbiome versus nutrition in affecting responses to immunotherapy, and whether chemotherapy is immunostimulatory or immunosuppressive. Discussion of these important topics are summarized in this report.

Keywords: CTLA-4 antigen; chimeric antigen; cytotoxicity; immunologic; immunotherapy; receptors.

Other Links

Free PMC article
Full text on Journal for immunotherapy of cancer

References
Cited By

References
Adoptive cell transfer therapy following non-myeloablative but lymphodepleting chemotherapy for the treatment of patients with refractory metastatic melanoma. Mark E Dudley, John R Wunderlich, +18 authors, Steven A Rosenberg. less J Clin Oncol, 2005 Apr 01; 23(10). PMID: 15800326 Free PMC article. Highly Cited.
CAR T Cells in Solid Tumors: Blueprints for Building Effective Therapies. Hannah M Knochelmann, Aubrey S Smith, +3 authors, Chrystal M Paulos. less Front Immunol, 2018 Aug 25; 9. PMID: 30140266 Free PMC article. Highly Cited. Review.
Chemotherapeutic targeting of cancer-induced immunosuppressive cells. Darya Alizadeh, Nicolas Larmonier. Cancer Res, 2014 Apr 30; 74(10). PMID: 24778417 Free PMC article. Highly Cited. Review.
Chimeric Antigen Receptor-T Cells for Targeting Solid Tumors: Current Challenges and Existing Strategies. Lorraine Springuel, Caroline Lonez, +14 authors, Frédéric F Lehmann. less BioDrugs, 2019 Aug 01; 33(5). PMID: 31363930 Free PMC article. Review.
Duration of Adjuvant Chemotherapy for Stage III Colon Cancer. Axel Grothey, Alberto F Sobrero, +20 authors, Timothy Iveson. less N Engl J Med, 2018 Mar 29; 378(13). PMID: 29590544 Free PMC article. Highly Cited.
CTLA4 blockade and GM-CSF combination immunotherapy alters the intratumor balance of effector and regulatory T cells. Sergio A Quezada, Karl S Peggs, Michael A Curran, James P Allison. J Clin Invest, 2006 Jun 17; 116(7). PMID: 16778987 Free PMC article. Highly Cited.
Dabrafenib in patients with Val600Glu or Val600Lys BRAF-mutant melanoma metastatic to the brain (BREAK-MB): a multicentre, open-label, phase 2 trial. Georgina V Long, Uwe Trefzer, +19 authors, Dirk Schadendorf. less Lancet Oncol, 2012 Oct 12; 13(11). PMID: 23051966 Highly Cited.
Combined Nivolumab and Ipilimumab in Melanoma Metastatic to the Brain. Hussein A Tawbi, Peter A Forsyth, +19 authors, Kim Margolin. less N Engl J Med, 2018 Aug 23; 379(8). PMID: 30134131 Free PMC article. Highly Cited.
International validation of the consensus Immunoscore for the classification of colon cancer: a prognostic and accuracy study. Franck Pagès, Bernhard Mlecnik, +96 authors, Jérôme Galon. less Lancet, 2018 May 15; 391(10135). PMID: 29754777 Highly Cited.
A defined commensal consortium elicits CD8 T cells and anti-cancer immunity. Takeshi Tanoue, Satoru Morita, +25 authors, Kenya Honda. less Nature, 2019 Jan 25; 565(7741). PMID: 30675064 Highly Cited.
Tumor regression in patients with metastatic synovial cell sarcoma and melanoma using genetically engineered lymphocytes reactive with NY-ESO-1. Paul F Robbins, Richard A Morgan, +18 authors, Steven A Rosenberg. less J Clin Oncol, 2011 Feb 02; 29(7). PMID: 21282551 Free PMC article. Highly Cited.
Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Jérôme Galon, Anne Costes, +13 authors, Franck Pagès. less Science, 2006 Sep 30; 313(5795). PMID: 17008531 Highly Cited.
Clinical efficacy and biomarker analysis of neoadjuvant atezolizumab in operable urothelial carcinoma in the ABACUS trial. Thomas Powles, Mark Kockx, +22 authors, Daniel Castellano. less Nat Med, 2019 Nov 07; 25(11). PMID: 31686036
The immunological effects of taxanes. O T Chan, L X Yang. Cancer Immunol Immunother, 2000 Aug 15; 49(4-5). PMID: 10941900 Review.
Adjuvant low-dose interferon {alpha}2a with or without dacarbazine compared with surgery alone: a prospective-randomized phase III DeCOG trial in melanoma patients with regional lymph node metastasis. C Garbe, P Radny, +8 authors, A Hauschild. less Ann Oncol, 2008 Feb 19; 19(6). PMID: 18281266
Optimized T-cell receptor-mimic chimeric antigen receptor T cells directed toward the intracellular Wilms Tumor 1 antigen. S Rafiq, T J Purdon, +5 authors, R J Brentjens. less Leukemia, 2016 Dec 08; 31(8). PMID: 27924074 Free PMC article.
Molecular Profiling Reveals Unique Immune and Metabolic Features of Melanoma Brain Metastases. Grant M Fischer, Ali Jalali, +31 authors, Michael A Davies. less Cancer Discov, 2019 Feb 23; 9(5). PMID: 30787016 Free PMC article. Highly Cited.
Dabrafenib plus trametinib in patients with BRAFV600-mutant melanoma brain metastases (COMBI-MB): a multicentre, multicohort, open-label, phase 2 trial. Michael A Davies, Philippe Saiag, +17 authors, Georgina V Long. less Lancet Oncol, 2017 Jun 09; 18(7). PMID: 28592387 Free PMC article. Highly Cited.
PD-1 blockade induces responses by inhibiting adaptive immune resistance. Paul C Tumeh, Christina L Harview, +23 authors, Antoni Ribas. less Nature, 2014 Nov 28; 515(7528). PMID: 25428505 Free PMC article. Highly Cited.
Chemotherapy-Induced IL34 Enhances Immunosuppression by Tumor-Associated Macrophages and Mediates Survival of Chemoresistant Lung Cancer Cells. Muhammad Baghdadi, Haruka Wada, +13 authors, Ken-Ichiro Seino. less Cancer Res, 2016 Aug 24; 76(20). PMID: 27550451
Clinical development of CAR T cells-challenges and opportunities in translating innovative treatment concepts. Jessica Hartmann, Martina Schüßler-Lenz, Attilio Bondanza, Christian J Buchholz. EMBO Mol Med, 2017 Aug 03; 9(9). PMID: 28765140 Free PMC article. Highly Cited. Review.
Ipilimumab in patients with melanoma and brain metastases: an open-label, phase 2 trial. Kim Margolin, Marc S Ernstoff, +12 authors, F Stephen Hodi. less Lancet Oncol, 2012 Mar 30; 13(5). PMID: 22456429 Highly Cited.
Dabrafenib in patients with melanoma, untreated brain metastases, and other solid tumours: a phase 1 dose-escalation trial. Gerald S Falchook, Georgina V Long, +14 authors, Richard F Kefford. less Lancet, 2012 May 23; 379(9829). PMID: 22608338 Free PMC article. Highly Cited.
Increased circulating myeloid-derived suppressor cells correlate with clinical cancer stage, metastatic tumor burden, and doxorubicin-cyclophosphamide chemotherapy. C Marcela Diaz-Montero, Mohamed Labib Salem, +3 authors, Alberto J Montero. less Cancer Immunol Immunother, 2008 May 01; 58(1). PMID: 18446337 Free PMC article. Highly Cited.
Immunosuppressive myeloid cells induced by chemotherapy attenuate antitumor CD4+ T-cell responses through the PD-1-PD-L1 axis. Zhi-Chun Ding, Xiaoyun Lu, +11 authors, Gang Zhou. less Cancer Res, 2014 May 02; 74(13). PMID: 24780756 Free PMC article.
Linking long-term dietary patterns with gut microbial enterotypes. Gary D Wu, Jun Chen, +15 authors, James D Lewis. less Science, 2011 Sep 03; 334(6052). PMID: 21885731 Free PMC article. Highly Cited.
Effect of miR-513a-5p on etoposide-stimulating B7-H1 expression in retinoblastoma cells. Li Wu, Zhen Chen, Jian Zhang, Yiqiao Xing. J Huazhong Univ Sci Technolog Med Sci, 2012 Aug 14; 32(4). PMID: 22886978
Distant intracranial failure in melanoma brain metastases treated with stereotactic radiosurgery in the era of immunotherapy and targeted agents. Sahaja Acharya, Mustafaa Mahmood, +12 authors, Christopher Abraham. less Adv Radiat Oncol, 2017 Dec 06; 2(4). PMID: 29204524 Free PMC article.
The commensal microbiome is associated with anti-PD-1 efficacy in metastatic melanoma patients. Vyara Matson, Jessica Fessler, +5 authors, Thomas F Gajewski. less Science, 2018 Jan 06; 359(6371). PMID: 29302014 Free PMC article. Highly Cited.
Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients. V Gopalakrishnan, C N Spencer, +67 authors, J A Wargo. less Science, 2017 Nov 04; 359(6371). PMID: 29097493 Free PMC article. Highly Cited.
Fat, fibre and cancer risk in African Americans and rural Africans. Stephen J D O'Keefe, Jia V Li, +21 authors, Erwin G Zoetendal. less Nat Commun, 2015 Apr 29; 6. PMID: 25919227 Free PMC article. Highly Cited.
Commensal Bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1 efficacy. Ayelet Sivan, Leticia Corrales, +9 authors, Thomas F Gajewski. less Science, 2015 Nov 07; 350(6264). PMID: 26541606 Free PMC article. Highly Cited.
Delivery of interferon-alpha transfected dendritic cells into central nervous system tumors enhances the antitumor efficacy of peripheral peptide-based vaccines. Hideho Okada, Takahiko Tsugawa, +11 authors, Ian F Pollack. less Cancer Res, 2004 Aug 18; 64(16). PMID: 15313927
Ipilimumab-dependent cell-mediated cytotoxicity of regulatory T cells ex vivo by nonclassical monocytes in melanoma patients. Emanuela Romano, Monika Kusio-Kobialka, +7 authors, Daniel E Speiser. less Proc Natl Acad Sci U S A, 2015 Apr 29; 112(19). PMID: 25918390 Free PMC article. Highly Cited.
Chimeric Antigen Receptor T Cell-Mediated Neurotoxicity in Nonhuman Primates. Agne Taraseviciute, Victor Tkachev, +20 authors, Michael C Jensen. less Cancer Discov, 2018 Mar 23; 8(6). PMID: 29563103 Free PMC article. Highly Cited.
Immunological Mechanisms Underneath the Efficacy of Cancer Therapy. Lorenzo Galluzzi, Laurence Zitvogel, Guido Kroemer. Cancer Immunol Res, 2016 Nov 03; 4(11). PMID: 27803050 Highly Cited. Review.
Chemotherapy induces enrichment of CD47+/CD73+/PDL1+ immune evasive triple-negative breast cancer cells. Debangshu Samanta, Youngrok Park, +5 authors, Gregg L Semenza. less Proc Natl Acad Sci U S A, 2018 Jan 26; 115(6). PMID: 29367423 Free PMC article. Highly Cited.
Anti-CTLA-4 Immunotherapy Does Not Deplete FOXP3+ Regulatory T Cells (Tregs) in Human Cancers. Anu Sharma, Sumit K Subudhi, +6 authors, Padmanee Sharma. less Clin Cancer Res, 2018 Jul 29; 25(4). PMID: 30054281 Free PMC article. Highly Cited.
Lymphocyte depletion and repopulation after chemotherapy for primary breast cancer. Rashmi Verma, Ruth E Foster, +5 authors, Clive R D Carter. less Breast Cancer Res, 2016 Jan 27; 18(1). PMID: 26810608 Free PMC article.
Fc-dependent depletion of tumor-infiltrating regulatory T cells co-defines the efficacy of anti-CTLA-4 therapy against melanoma. Tyler R Simpson, Fubin Li, +11 authors, Sergio A Quezada. less J Exp Med, 2013 Jul 31; 210(9). PMID: 23897981 Free PMC article. Highly Cited.
Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors. Bertrand Routy, Emmanuelle Le Chatelier, +45 authors, Laurence Zitvogel. less Science, 2017 Nov 04; 359(6371). PMID: 29097494 Highly Cited.
Cancer regression and neurological toxicity following anti-MAGE-A3 TCR gene therapy. Richard A Morgan, Nachimuthu Chinnasamy, +28 authors, Steven A Rosenberg. less J Immunother, 2013 Feb 05; 36(2). PMID: 23377668 Free PMC article. Highly Cited.
Bleomycin exerts ambivalent antitumor immune effect by triggering both immunogenic cell death and proliferation of regulatory T cells. Hélène Bugaut, Mélanie Bruchard, +10 authors, Grégoire Mignot. less PLoS One, 2013 Jun 14; 8(6). PMID: 23762310 Free PMC article.
The engagement of CTLA-4 on primary melanoma cell lines induces antibody-dependent cellular cytotoxicity and TNF-α production. Stefania Laurent, Paola Queirolo, +15 authors, Maria Pia Pistillo. less J Transl Med, 2013 May 03; 11. PMID: 23634660 Free PMC article.
Tumor-specific killer cells in paraneoplastic cerebellar degeneration. M L Albert, J C Darnell, +3 authors, A Bender, L M Francisco, N Bhardwaj, R B Darnell. less Nat Med, 1998 Nov 11; 4(11). PMID: 9809559
Sequestration of T cells in bone marrow in the setting of glioblastoma and other intracranial tumors. Pakawat Chongsathidkiet, Christina Jackson, +20 authors, Peter E Fecci. less Nat Med, 2018 Aug 15; 24(9). PMID: 30104766 Free PMC article. Highly Cited.
Pembrolizumab for patients with melanoma or non-small-cell lung cancer and untreated brain metastases: early analysis of a non-randomised, open-label, phase 2 trial. Sarah B Goldberg, Scott N Gettinger, +18 authors, Harriet M Kluger. less Lancet Oncol, 2016 Jun 09; 17(7). PMID: 27267608 Free PMC article. Highly Cited.
Cellular immune profile of patients with advanced cancer before and after taxane treatment. A W Tong, B Seamour, +7 authors, J Nemunaitis. less Am J Clin Oncol, 2000 Oct 20; 23(5). PMID: 11039505

Citedby
Pharmacology-based ranking of anti-cancer drugs to guide clinical development of cancer immunotherapy combinations. Vincent Lemaire, Colby S Shemesh, Anand Rotte. J Exp Clin Cancer Res, 2021 Oct 03; 40(1). PMID: 34598713 Free PMC article. Review.

BioKDE: Biomedical Knowledge Discovery Engine

Abstract

Other Links