Journal Article
. 2018 Jun; 7(6):e1431088.
doi: 10.1080/2162402X.2018.1431088.

RANKL blockade improves efficacy of PD1-PD-L1 blockade or dual PD1-PD-L1 and CTLA4 blockade in mouse models of cancer

Elizabeth Ahern 1 Heidi Harjunpää 2 Jake S O'Donnell 1 Stacey Allen 2 William C Dougall 1 Michele W L Teng 2 Mark J Smyth 1 
Affiliations
  • PMID: 29872559
  •     50 References
  •     37 citations

Abstract

Receptor activator of NF-κB ligand (RANKL) and its receptor RANK, are members of the tumor necrosis factor and receptor superfamilies, respectively. Antibodies targeting RANKL have recently been evaluated in combination with anti-CTLA4 in case reports of human melanoma and mouse models of cancer. However, the efficacy of anti-RANKL in combination with antibodies targeting other immune checkpoint receptors such as PD1 has not been reported. In this study, we demonstrated that blockade of RANKL improves anti-metastatic activity of antibodies targeting PD1/PD-L1 and improves subcutaneous growth suppression in mouse models of melanoma, prostate and colon cancer. Suppression of experimental lung metastasis following combination anti-RANKL with anti-PD1 requires NK cells and IFN-γ, whereas subcutaneous tumor growth suppression with this combination therapy is attenuated in the absence of T cells and IFN-γ. Furthermore, addition of anti-RANKL to anti-PD1 and anti-CTLA4 resulted in superior anti-tumor responses, irrespective of the ability of anti-CTLA4 isotype to engage activating FcR, and concurrent or delayed RANKL blockade was most effective. Early-during-treatment assessment reveals this triple combination therapy compared to dual anti-PD1 and anti-CTLA4 combination therapy further increased the proportion of tumor-infiltrating CD4+ and CD8+ T cells that can produce both IFN-γ and TNF. Finally, RANKL expression appears to identify tumor-specific CD8+ T cells expressing higher levels of PD1 which can be modulated by anti-PD1. These data set the scene for clinical evaluation of denosumab use in patients receiving contemporary immune checkpoint blockade.

Keywords: CD8+ T cells; RANK; RANKL; metastasis; tumors.

Mouse models of prostate cancer.
P Sharma, N Schreiber-Agus.
Oncogene, 1999 Sep 28; 18(38). PMID: 10498888
Review.
Stromal infrastructure of the lymph node and coordination of immunity.
Jonathan E Chang, Shannon J Turley.
Trends Immunol, 2014 Dec 17; 36(1). PMID: 25499856
Review.
Anti-CTLA-4 antibodies of IgG2a isotype enhance antitumor activity through reduction of intratumoral regulatory T cells.
Mark J Selby, John J Engelhardt, +4 authors, Alan J Korman.
Cancer Immunol Res, 2014 Apr 30; 1(1). PMID: 24777248
Highly Cited.
Regulation of activation-induced receptor activator of NF-kappaB ligand (RANKL) expression in T cells.
Ruoxiang Wang, Liying Zhang, +4 authors, Yufang Shi.
Eur J Immunol, 2002 Mar 29; 32(4). PMID: 11920576
The TRAMP mouse as a model for prostate cancer.
A A Hurwitz, B A Foster, +2 authors, E D Kwon.
Curr Protoc Immunol, 2008 Apr 25; Chapter 20. PMID: 18432778
Rapid complete response of metastatic melanoma in a patient undergoing ipilimumab immunotherapy in the setting of active ulcerative colitis.
A Doran Bostwick, April K Salama, Brent A Hanks.
J Immunother Cancer, 2015 May 21; 3. PMID: 25992290    Free PMC article.
Analysis of Immune Signatures in Longitudinal Tumor Samples Yields Insight into Biomarkers of Response and Mechanisms of Resistance to Immune Checkpoint Blockade.
Pei-Ling Chen, Whijae Roh, +41 authors, Jennifer A Wargo.
Cancer Discov, 2016 Jun 16; 6(8). PMID: 27301722    Free PMC article.
Highly Cited.
A Threshold Level of Intratumor CD8+ T-cell PD1 Expression Dictates Therapeutic Response to Anti-PD1.
Shin Foong Ngiow, Arabella Young, +4 authors, Mark J Smyth.
Cancer Res, 2015 Jul 26; 75(18). PMID: 26208901
Highly Cited.
Preclinical Development of Ipilimumab and Nivolumab Combination Immunotherapy: Mouse Tumor Models, In Vitro Functional Studies, and Cynomolgus Macaque Toxicology.
Mark J Selby, John J Engelhardt, +11 authors, Alan J Korman.
PLoS One, 2016 Sep 10; 11(9). PMID: 27610613    Free PMC article.
Highly Cited.
Characterization of prostatic epithelial cell lines derived from transgenic adenocarcinoma of the mouse prostate (TRAMP) model.
B A Foster, J R Gingrich, +2 authors, N M Greenberg.
Cancer Res, 1997 Aug 15; 57(16). PMID: 9269988
Highly Cited.
Randomized phase II trial of denosumab in patients with bone metastases from prostate cancer, breast cancer, or other neoplasms after intravenous bisphosphonates.
Karim Fizazi, Allan Lipton, +7 authors, Susie Jun.
J Clin Oncol, 2009 Feb 25; 27(10). PMID: 19237632
Highly Cited.
Combination cancer immunotherapies tailored to the tumour microenvironment.
Mark J Smyth, Shin Foong Ngiow, Antoni Ribas, Michele W L Teng.
Nat Rev Clin Oncol, 2015 Nov 26; 13(3). PMID: 26598942
Highly Cited. Review.
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.
T cell exhaustion.
E John Wherry.
Nat Immunol, 2011 Jul 09; 12(6). PMID: 21739672
Highly Cited. Review.
Safety and clinical activity of pembrolizumab for treatment of recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-012): an open-label, multicentre, phase 1b trial.
Tanguy Y Seiwert, Barbara Burtness, +9 authors, Laura Q Chow.
Lancet Oncol, 2016 Jun 02; 17(7). PMID: 27247226
Highly Cited.
Randomized, double-blind study of denosumab versus zoledronic acid in the treatment of bone metastases in patients with advanced cancer (excluding breast and prostate cancer) or multiple myeloma.
David H Henry, Luis Costa, +15 authors, Howard Yeh.
J Clin Oncol, 2011 Feb 24; 29(9). PMID: 21343556
Highly Cited.
Denosumab and bone-metastasis-free survival in men with castration-resistant prostate cancer: results of a phase 3, randomised, placebo-controlled trial.
Matthew R Smith, Fred Saad, +18 authors, Carsten Goessl.
Lancet, 2011 Nov 19; 379(9810). PMID: 22093187    Free PMC article.
Highly Cited.
PD-1 blockade with nivolumab in relapsed or refractory Hodgkin's lymphoma.
Stephen M Ansell, Alexander M Lesokhin, +16 authors, Philippe Armand.
N Engl J Med, 2014 Dec 09; 372(4). PMID: 25482239    Free PMC article.
Highly Cited.
Targeting RANKL in metastasis.
William C Dougall, Ingunn Holen, Eva González Suárez.
Bonekey Rep, 2014 May 06; 3. PMID: 24795813    Free PMC article.
Review.
Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma.
Robert J Motzer, Bernard Escudier, +25 authors, CheckMate 025 Investigators.
N Engl J Med, 2015 Sep 26; 373(19). PMID: 26406148    Free PMC article.
Highly Cited.
Overall Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma.
Jedd D Wolchok, Vanna Chiarion-Sileni, +30 authors, James Larkin.
N Engl J Med, 2017 Sep 12; 377(14). PMID: 28889792    Free PMC article.
Highly Cited.
Bench to bedside: elucidation of the OPG-RANK-RANKL pathway and the development of denosumab.
David L Lacey, William J Boyle, +5 authors, Roger Dansey.
Nat Rev Drug Discov, 2012 May 01; 11(5). PMID: 22543469
Highly Cited. Review.
Blockade of CTLA-4 on both effector and regulatory T cell compartments contributes to the antitumor activity of anti-CTLA-4 antibodies.
Karl S Peggs, Sergio A Quezada, +2 authors, James P Allison.
J Exp Med, 2009 Jul 08; 206(8). PMID: 19581407    Free PMC article.
Highly Cited.
Prostate cancer in a transgenic mouse.
N M Greenberg, F DeMayo, +7 authors, J M Rosen.
Proc Natl Acad Sci U S A, 1995 Apr 11; 92(8). PMID: 7724580    Free PMC article.
Highly Cited.
Nivolumab in previously untreated melanoma without BRAF mutation.
Caroline Robert, Georgina V Long, +25 authors, Paolo A Ascierto.
N Engl J Med, 2014 Nov 18; 372(4). PMID: 25399552
Highly Cited.
TRANCE is a novel ligand of the tumor necrosis factor receptor family that activates c-Jun N-terminal kinase in T cells.
B R Wong, J Rho, +9 authors, Y Choi.
J Biol Chem, 1997 Oct 06; 272(40). PMID: 9312132
Highly Cited.
Co-administration of RANKL and CTLA4 Antibodies Enhances Lymphocyte-Mediated Antitumor Immunity in Mice.
Elizabeth Ahern, Heidi Harjunpää, +7 authors, Mark J Smyth.
Clin Cancer Res, 2017 Jun 22; 23(19). PMID: 28634284
Impact of tumour microenvironment and Fc receptors on the activity of immunomodulatory antibodies.
Andrew J S Furness, Frederick Arce Vargas, Karl S Peggs, Sergio A Quezada.
Trends Immunol, 2014 Jun 24; 35(7). PMID: 24953012
Review.
Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer.
Martin Reck, Delvys Rodríguez-Abreu, +16 authors, KEYNOTE-024 Investigators.
N Engl J Med, 2016 Oct 11; 375(19). PMID: 27718847
Highly Cited.
Interleukin-12 from CD103+ Batf3-Dependent Dendritic Cells Required for NK-Cell Suppression of Metastasis.
Deepak Mittal, Dipti Vijayan, +9 authors, Mark J Smyth.
Cancer Immunol Res, 2017 Oct 27; 5(12). PMID: 29070650
Pembrolizumab versus Ipilimumab in Advanced Melanoma.
Caroline Robert, Jacob Schachter, +20 authors, KEYNOTE-006 investigators.
N Engl J Med, 2015 Apr 22; 372(26). PMID: 25891173
Highly Cited.
Dynamic Changes in PD-L1 Expression and Immune Infiltrates Early During Treatment Predict Response to PD-1 Blockade in Melanoma.
Ricardo E Vilain, Alexander M Menzies, +15 authors, Richard A Scolyer.
Clin Cancer Res, 2017 May 18; 23(17). PMID: 28512174
Highly Cited.
Progression to androgen insensitivity in a novel in vitro mouse model for prostate cancer.
P A Baley, K Yoshida, +2 authors, T C Thompson.
J Steroid Biochem Mol Biol, 1995 May 01; 52(5). PMID: 7538321
Nivolumab versus chemotherapy in patients with advanced melanoma who progressed after anti-CTLA-4 treatment (CheckMate 037): a randomised, controlled, open-label, phase 3 trial.
Jeffrey S Weber, Sandra P D'Angelo, +25 authors, James Larkin.
Lancet Oncol, 2015 Mar 22; 16(4). PMID: 25795410
Highly Cited.
Randomized active-controlled phase II study of denosumab efficacy and safety in patients with breast cancer-related bone metastases.
Allan Lipton, Guenther G Steger, +13 authors, Susie Jun.
J Clin Oncol, 2007 Sep 06; 25(28). PMID: 17785705
Denosumab compared with zoledronic acid for the treatment of bone metastases in patients with advanced breast cancer: a randomized, double-blind study.
Alison T Stopeck, Allan Lipton, +12 authors, Ada Braun.
J Clin Oncol, 2010 Nov 10; 28(35). PMID: 21060033
Highly Cited.
Amelioration of bone loss in collagen-induced arthritis by neutralizing anti-RANKL monoclonal antibody.
Seiji Kamijo, Atsuo Nakajima, +5 authors, Ko Okumura.
Biochem Biophys Res Commun, 2006 Jul 04; 347(1). PMID: 16815304
RANKL expression in normal and malignant breast tissue responds to progesterone and is up-regulated during the luteal phase.
Hong Hu, Jun Wang, +8 authors, Seema A Khan.
Breast Cancer Res Treat, 2014 Jul 11; 146(3). PMID: 25007964
Co-inhibition of CD73 and A2AR Adenosine Signaling Improves Anti-tumor Immune Responses.
Arabella Young, Shin Foong Ngiow, +9 authors, Mark J Smyth.
Cancer Cell, 2016 Sep 14; 30(3). PMID: 27622332
Highly Cited.
Role of RANKL and RANK in bone loss and arthritis.
D Holstead Jones, Y-Y Kong, J M Penninger.
Ann Rheum Dis, 2002 Oct 16; 61 Suppl 2. PMID: 12379618    Free PMC article.
Review.
Suppression of Metastases Using a New Lymphocyte Checkpoint Target for Cancer Immunotherapy.
Stephen J Blake, Kimberley Stannard, +15 authors, Mark J Smyth.
Cancer Discov, 2016 Jan 21; 6(4). PMID: 26787820
Highly Cited.
Timing of PD-1 Blockade Is Critical to Effective Combination Immunotherapy with Anti-OX40.
David J Messenheimer, Shawn M Jensen, +6 authors, Bernard A Fox.
Clin Cancer Res, 2017 Sep 01; 23(20). PMID: 28855348    Free PMC article.
Highly Cited.
The immunoreceptor TIGIT regulates antitumor and antiviral CD8(+) T cell effector function.
Robert J Johnston, Laetitia Comps-Agrar, +9 authors, Jane L Grogan.
Cancer Cell, 2014 Dec 04; 26(6). PMID: 25465800
Highly Cited.
Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma.
James Larkin, Vanna Chiarion-Sileni, +28 authors, Jedd D Wolchok.
N Engl J Med, 2015 Jun 02; 373(1). PMID: 26027431    Free PMC article.
Highly Cited.
Kinetics of costimulatory molecule expression by T cells and dendritic cells during the induction of tolerance versus immunity in vivo.
Kristin Hochweller, Stephen M Anderton.
Eur J Immunol, 2005 Mar 10; 35(4). PMID: 15756642
Overall survival improvement in patients with lung cancer and bone metastases treated with denosumab versus zoledronic acid: subgroup analysis from a randomized phase 3 study.
Giorgio Vittorio Scagliotti, Vera Hirsh, +16 authors, Ira Jacobs.
J Thorac Oncol, 2012 Nov 17; 7(12). PMID: 23154554
Negative immune checkpoint regulation by VISTA: a mechanism of acquired resistance to anti-PD-1 therapy in metastatic melanoma patients.
Hojabr Kakavand, Louise A Jackett, +7 authors, Richard A Scolyer.
Mod Pathol, 2017 Aug 05; 30(12). PMID: 28776578
Resistance to PD1/PDL1 checkpoint inhibition.
Jake S O'Donnell, Georgina V Long, +2 authors, Mark J Smyth.
Cancer Treat Rev, 2016 Dec 13; 52. PMID: 27951441
Highly Cited. Review.
Osteoclasts promote immune suppressive microenvironment in multiple myeloma: therapeutic implication.
Gang An, Chirag Acharya, +7 authors, Kenneth C Anderson.
Blood, 2016 Jul 16; 128(12). PMID: 27418644    Free PMC article.
Highly Cited.
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.
J Exp Med, 2013 Jul 31; 210(9). PMID: 23897981    Free PMC article.
Highly Cited.
Osteoclast Immunosuppressive Effects in Multiple Myeloma: Role of Programmed Cell Death Ligand 1.
Yu-Tzu Tai, Shih-Feng Cho, Kenneth C Anderson.
Front Immunol, 2018 Aug 28; 9. PMID: 30147691    Free PMC article.
Review.
An observational study of concomitant immunotherapies and denosumab in patients with advanced melanoma or lung cancer.
Alexander Liede, Rohini K Hernandez, +5 authors, Mark J Smyth.
Oncoimmunology, 2018 Dec 14; 7(12). PMID: 30524886    Free PMC article.
Dual targeting of RANKL and PD-1 with a bispecific antibody improves anti-tumor immunity.
William C Dougall, Amelia Roman Aguilera, Mark J Smyth.
Clin Transl Immunology, 2019 Oct 02; 8(10). PMID: 31572609    Free PMC article.
Successful Treatment of Multiple Metastatic Melanoma with Nivolumab, Ipilimumab plus Denosumab Combined Therapy.
Saaya Yoshida, Taku Fujimura, +3 authors, Setsuya Aiba.
Case Rep Oncol, 2019 Nov 26; 12(3). PMID: 31762756    Free PMC article.
Pharmacodynamics of Pre-Operative PD1 checkpoint blockade and receptor activator of NFkB ligand (RANKL) inhibition in non-small cell lung cancer (NSCLC): study protocol for a multicentre, open-label, phase 1B/2, translational trial (POPCORN).
Elizabeth Ahern, Annette Cubitt, +7 authors, Brett G M Hughes.
Trials, 2019 Dec 21; 20(1). PMID: 31856909    Free PMC article.
Predictive biomarkers and mechanisms underlying resistance to PD1/PD-L1 blockade cancer immunotherapy.
Daixi Ren, Yuze Hua, +17 authors, Wei Xiong.
Mol Cancer, 2020 Feb 01; 19(1). PMID: 32000802    Free PMC article.
Review.
CD96 Is an Immune Checkpoint That Regulates CD8+ T-cell Antitumor Function.
Deepak Mittal, Ailin Lepletier, +16 authors, Mark J Smyth.
Cancer Immunol Res, 2019 Mar 22; 7(4). PMID: 30894377    Free PMC article.
Pulling RANK on Cancer: Blocking Aire-Mediated Central Tolerance to Enhance Immunotherapy.
Maureen A Su, Mark S Anderson.
Cancer Immunol Res, 2019 Jun 05; 7(6). PMID: 31160305    Free PMC article.
Review.
The RANKL-RANK Axis: A Bone to Thymus Round Trip.
Cristina Sobacchi, Ciro Menale, Anna Villa.
Front Immunol, 2019 Apr 16; 10. PMID: 30984193    Free PMC article.
Review.
Successful Treatment of a Patient with anti-PD1 Antibody-Resistant Advanced Mucosal Melanoma with Nivolumab, Ipilimumab plus Denosumab Combination Therapy.
Taku Fujimura, Yumi Kambayashi, +5 authors, Setsuya Aiba.
Case Rep Oncol, 2020 Apr 21; 13(1). PMID: 32308589    Free PMC article.
Targeting the RANKL/RANK/OPG Axis for Cancer Therapy.
Jie Ming, Shane J F Cronin, Josef M Penninger.
Front Oncol, 2020 Aug 28; 10. PMID: 32850393    Free PMC article.
Review.
Trial Watch: experimental TLR7/TLR8 agonists for oncological indications.
Giorgio Frega, Qi Wu, +4 authors, Oliver Kepp.
Oncoimmunology, 2020 Sep 17; 9(1). PMID: 32934889    Free PMC article.
Review.
Baseline Absolute Lymphocyte Count and ECOG Performance Score Are Associated with Survival in Advanced Non-Small Cell Lung Cancer Undergoing PD-1/PD-L1 Blockade.
Florian Huemer, David Lang, +7 authors, Richard Greil.
J Clin Med, 2019 Jul 13; 8(7). PMID: 31295966    Free PMC article.
Treatment of Advanced Melanoma: Past, Present and Future.
Taku Fujimura, Yumi Kambayashi, +2 authors, Setsuya Aiba.
Life (Basel), 2020 Sep 20; 10(9). PMID: 32948031    Free PMC article.
Review.
The Role of the RANKL/RANK Axis in the Prevention and Treatment of Breast Cancer with Immune Checkpoint Inhibitors and Anti-RANKL.
Aristofania Simatou, Panagiotis Sarantis, +2 authors, Michalis V Karamouzis.
Int J Mol Sci, 2020 Oct 18; 21(20). PMID: 33066388    Free PMC article.
Review.
Challenges in Combining Immunotherapy with Radiotherapy in Recurrent/Metastatic Head and Neck Cancer.
Gaber Plavc, Tanja Jesenko, Miha Oražem, Primož Strojan.
Cancers (Basel), 2020 Nov 05; 12(11). PMID: 33143094    Free PMC article.
Review.
The RANK-RANKL axis: an opportunity for drug repurposing in cancer?
S Peters, P Clézardin, +2 authors, C Gedye.
Clin Transl Oncol, 2019 Jan 19; 21(8). PMID: 30656607
Review.
RANK-RANKL Signaling in Cancer of the Uterine Cervix: A Review.
Peter A van Dam, Yannick Verhoeven, +11 authors, Xuan Bich Trinh.
Int J Mol Sci, 2019 May 06; 20(9). PMID: 31052546    Free PMC article.
Review.
RANKL-Targeted Combination Therapy with Osteoprotegerin Variant Devoid of TRAIL Binding Exerts Biphasic Effects on Skeletal Remodeling and Antitumor Immunity.
Hong Wang, Reading Ashton, +5 authors, Selvarangan Ponnazhagan.
Mol Cancer Ther, 2020 Nov 18; 19(12). PMID: 33199500    Free PMC article.
Inhibition of RANK signaling in breast cancer induces an anti-tumor immune response orchestrated by CD8+ T cells.
Clara Gómez-Aleza, Bastien Nguyen, +31 authors, Eva González-Suárez.
Nat Commun, 2020 Dec 12; 11(1). PMID: 33303745    Free PMC article.
Role of RANKL in cancer development and metastasis.
Kazuo Okamoto.
J Bone Miner Metab, 2021 Jan 03; 39(1). PMID: 33387063
Review.
PD-1 Immune Checkpoint Inhibitor Therapy Malignant Tumor Based on Monotherapy and Combined Treatment Research.
Yu Zhang, Guang-Ze Mou, +7 authors, Cheng-Hao Jin.
Technol Cancer Res Treat, 2021 Mar 25; 20. PMID: 33759637    Free PMC article.
Review.
Immuno-PET Molecular Imaging of RANKL in Cancer.
Jonatan Dewulf, Christel Vangestel, +5 authors, Tim Van den Wyngaert.
Cancers (Basel), 2021 May 06; 13(9). PMID: 33946410    Free PMC article.
The roles of PD-1/PD-L1 in the prognosis and immunotherapy of prostate cancer.
Yichi Xu, Gendi Song, +5 authors, Zhi-Wei Wang.
Mol Ther, 2021 May 02; 29(6). PMID: 33932597    Free PMC article.
Review.
Osteoimmuno-Oncology: Therapeutic Opportunities for Targeting Immune Cells in Bone Metastasis.
Tiina E Kähkönen, Jussi M Halleen, Jenni Bernoulli.
Cells, 2021 Jul 03; 10(6). PMID: 34204474    Free PMC article.
Review.
What Do We Have to Know about PD-L1 Expression in Prostate Cancer? A Systematic Literature Review. Part 5: Epigenetic Regulation of PD-L1.
Andrea Palicelli, Stefania Croci, +24 authors, Martina Bonacini.
Int J Mol Sci, 2021 Nov 28; 22(22). PMID: 34830196    Free PMC article.
Systematic Review.
What Do We Have to Know about PD-L1 Expression in Prostate Cancer? A Systematic Literature Review. Part 3: PD-L1, Intracellular Signaling Pathways and Tumor Microenvironment.
Andrea Palicelli, Stefania Croci, +24 authors, Martina Bonacini.
Int J Mol Sci, 2021 Nov 28; 22(22). PMID: 34830209    Free PMC article.
Systematic Review.
What Do We Have to Know about PD-L1 Expression in Prostate Cancer? A Systematic Literature Review. Part 2: Clinic-Pathologic Correlations.
Andrea Palicelli, Martina Bonacini, +26 authors, Moira Ragazzi.
Cells, 2021 Nov 28; 10(11). PMID: 34831388    Free PMC article.
Systematic Review.
What Do We Have to Know about PD-L1 Expression in Prostate Cancer? A Systematic Literature Review. Part 1: Focus on Immunohistochemical Results with Discussion of Pre-Analytical and Interpretation Variables.
Andrea Palicelli, Martina Bonacini, +26 authors, Magda Zanelli.
Cells, 2021 Nov 28; 10(11). PMID: 34831389    Free PMC article.
Systematic Review.
What Do We Have to Know about PD-L1 Expression in Prostate Cancer? A Systematic Literature Review. Part 4: Experimental Treatments in Pre-Clinical Studies (Cell Lines and Mouse Models).
Andrea Palicelli, Stefania Croci, +22 authors, Martina Bonacini.
Int J Mol Sci, 2021 Nov 28; 22(22). PMID: 34830179    Free PMC article.
Systematic Review.
Immune Checkpoint Inhibitor Therapy for Bone Metastases: Specific Microenvironment and Current Situation.
Chang Liu, Miao Wang, +4 authors, Zhiwei Wang.
J Immunol Res, 2021 Dec 09; 2021. PMID: 34877360    Free PMC article.
Review.
What Do We Have to Know about PD-L1 Expression in Prostate Cancer? A Systematic Literature Review. Part 7: PD-L1 Expression in Liquid Biopsy.
Andrea Palicelli, Martina Bonacini, +14 authors, Beatrice Melli.
J Pers Med, 2021 Dec 25; 11(12). PMID: 34945784    Free PMC article.
Review.
What Do We Have to Know about PD-L1 Expression in Prostate Cancer? A Systematic Literature Review (Part 6): Correlation of PD-L1 Expression with the Status of Mismatch Repair System, BRCA, PTEN, and Other Genes.
Andrea Palicelli, Stefania Croci, +21 authors, Martina Bonacini.
Biomedicines, 2022 Feb 26; 10(2). PMID: 35203446    Free PMC article.
Review.
Roles of the RANKL-RANK Axis in Immunity-Implications for Pathogenesis and Treatment of Bone Metastasis.
Bo Li, Pengru Wang, +3 authors, Pingting Zhou.
Front Immunol, 2022 Apr 08; 13. PMID: 35386705    Free PMC article.
Review.
Bispecific Antibodies Progression in Malignant Melanoma.
Juan Tang, Youling Gong, Xuelei Ma.
Front Pharmacol, 2022 Apr 12; 13. PMID: 35401191    Free PMC article.
Review.
The Therapeutic Effect and Clinical Outcome of Immune Checkpoint Inhibitors on Bone Metastasis in Advanced Non-Small-Cell Lung Cancer.
Yohei Asano, Norio Yamamoto, +13 authors, Hiroyuki Tsuchiya.
Front Oncol, 2022 Apr 19; 12. PMID: 35433422    Free PMC article.
RANKL biology.
Noriko Takegahara, Hyunsoo Kim, Yongwon Choi.
Bone, 2022 Feb 20; 159. PMID: 35181574    Free PMC article.
Review.