The Association of Programmed Death Ligand 1 (PD-L1) and Cluster of Differentiation 95 Ligand (CD95L) Immunoexpression with Chemotherapy Response in Classical Hodgkin Lymphoma
Background: Programmed Death Ligand (PD-L1) and Cluster of Differentiation 95 (CD95L) are influenced by oncogenes and function in the anti-apoptosis process which is thought to play a role in chemotherapy resistance. This study aimed to analyze the association of PD-L1 and CD95L immunoexpression with chemotherapy response in Classical Hodgkin Lymphoma (CHL).
Method: This study involved 40 cases of histopathologically diagnosed CHL treated with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) chemotherapy. PD-L1 and CD95L immunohistochemical staining were performed in selected paraffin-embedded tissue blocks of all cases. The chemotherapy response status of the patients was taken from the medical record
Results: High PDL-1 immunoexpression was evident in 19 (47.5%) cases while positive CD95L immunoexpression was found in 14 (35%) CHL cases. High PD-L1 immunoexpression was significantly associated with the Non-Responsive (NR) group (78.9%) with p-value = 0.0001. Positive CD95L immunoexpression was greater in the NR group (71.4%) with p-value = 0.37.
Conclusion: : High PD-L1 immunoexpression indicated an unfavorable response to ABVD chemotherapy in CHL. CD95L immunoexpression was not associated with ABVD chemotherapy response in CHL.
Swerdlow SH, Campo E, Haris NL, Jaffe ES, Pileri SA, Stein H, et al. Hodgkin Lymphoma. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues Lyon: International Agency for Research on Cancer Press. 2017;423-41.
Gerrie AS, Power MM, Shepherd JD, Savage KJ, Sehn LH, Connors JM. Chemoresistance can be overcome with high-dose chemotherapy and autologous stem-cell transplantation for relapsed and refractory Hodgkin lymphoma. Ann. Oncol. 2014 Nov;25(11):2218-23.
Jo Y, Choi N, Kim K, Koo HJ, Choi J, Kim HN. Chemoresistance of Cancer Cells: Requirements of Tumor Microenvironment-mimicking In Vitro Models in Anti-Cancer Drug Development. Theranostics. 2018;8(19):5259-75.
De Goycoechea D, Stalder G, Martins F, Duchosal MA. Immune Checkpoint Inhibition in Classical Hodgkin Lymphoma: From Early Achievements towards New Perspectives. J Oncol. 2019;2019:9513701.
Riella LV, Paterson AM, Sharpe AH, Chandraker A. Role of the PD-1 pathway in the immune response. Am J of Transplant. 2012 Oct;12(10):2575-87.
Dong P, Xiong Y, Yue J, Hanley SJB, Watari H. Tumor-Intrinsic PD-L1 Signaling in Cancer Initiation, Development and Treatment: Beyond Immune Evasion. Front Oncol. 2018;8:386.
Liu S, Chen S, Yuan W, Wang H, Chen K, Li D, et al. PD-1/PD-L1 interaction up-regulates MDR1/P-gp expression in breast cancer cells via PI3K/AKT and MAPK/ERK pathways. Oncotarget. 2017 Nov 21;8(59):99901-12.
Liu J, Quan L, Zhang C, Liu A, Tong D, Wang J. Over-activated PD-1/PD-L1 axis facilitates the chemoresistance of diffuse large B-cell lymphoma cells to the CHOP regimen. Oncol Lett. 2018 Mar;15(3):3321-8.
Ishibashi M, Tamura H, Sunakawa M, Kondo-Onodera A, Okuyama N, Hamada Y, et al. Myeloma Drug Resistance Induced by Binding of Myeloma B7-H1 (PD-L1) to PD-1. Cancer Immunol Res. 2016 Sep 2;4(9):779-88.
Villasboas JC, Ansell S. Checkpoint Inhibition: Programmed Cell Death 1 and Programmed Cell Death 1 Ligand Inhibitors in Hodgkin Lymphoma. Cancer J. 2016 Jan-Feb;22(1):17-22.
Lavrik IN, Krammer PH. Regulation of CD95/Fas signaling at the DISC. Cell Death Differ. 2012 Jan;19(1):36-41.
Houston A, O'Connell J. The Fas signalling pathway and its role in the pathogenesis of cancer. Curr Opin Pharmacol. 2004 Aug;4(4):321-6.
Peter ME, Hadji A, Murmann AE, Brockway S, Putzbach W, Pattanayak A, et al. The role of CD95 and CD95 ligand in cancer. Cell Death Differ. 2015 May;22(5):885-6.
Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009 Jan;45(2):228-47.
Hollander P, Kamper P, Smedby KE, Enblad G, Ludvigsen M, Mortensen J, et al. High proportions of PD-1(+) and PD-L1(+) leukocytes in classical Hodgkin lymphoma microenvironment are associated with inferior outcome. Blood Adv. 2017 Aug 8;1(18):1427-39.
de Carvalho-Neto PB, dos Santos M, de Carvalho MB, Mercante AM, Santos VP, Severino P, et al. FAS/FASL expression profile as a prognostic marker in squamous cell carcinoma of the oral cavity. PLoS One. 2013;8(7):e69024.
Aryanti, Hernowo B, Agustina H. Clinicopathologic Characteristics and Chemotherapy Response of Classic Hodgkin Lymphoma: A Study in Tertiary Teaching Hospital. Journal of Drug Delivery and Therapeutics. 2020 Dec;10:95-8.
Domínguez RA, Márquez A, Gumá J, Llanos M, Herrero J, Nieves MA, et al. Treatment of stage I and II Hodgkin's lymphoma with ABVD chemotherapy: results after 7 years of a prospective study. Ann Oncol. 2004 Dec;15(12):1798-804.
Canellos GP, Anderson JR, Propert KJ, Nissen N, Cooper MR, Henderson ES, et al. Chemotherapy of advanced Hodgkin's disease with MOPP, ABVD, or MOPP alternating with ABVD. New Engl J Medicine. 1992 Nov 19;327(21):1478-84.
Gordon LI, Hong F, Fisher RI, Bartlett NL, Connors JM, Gascoyne RD, et al. Randomized Phase III Trial of ABVD Versus Stanford V With or Without Radiation Therapy in Locally Extensive and Advanced-Stage Hodgkin Lymphoma: An Intergroup Study Coordinated by the Eastern Cooperative Oncology Group (E2496). J Clin Oncol. 2013;31(6):684-91.
Zhang P, Ma Y, Lv C, Huang M, Li M, Dong B, et al. Upregulation of programmed cell death ligand 1 promotes resistance response in non-small-cell lung cancer patients treated with neo-adjuvant chemotherapy. Cancer Sci. 2016 Nov;107(11):1563-71.
Bianchini G, Pusztai L, Pienkowski T, Im YH, Bianchi GV, Tseng LM, et al. Immune modulation of pathologic complete response after neoadjuvant HER2-directed therapies in the NeoSphere trial. Ann Oncol. 2015 Dec;26(12):2429-36.
Zhang P, Su DM, Liang M, Fu J. Chemopreventive agents induce programmed death-1-ligand 1 (PD-L1) surface expression in breast cancer cells and promote PD-L1-mediated T cell apoptosis. Molecular immunology. 2008 Mar;45(5):1470-6.
Meti N, Esfahani K, Johnson NA. The Role of Immune Checkpoint Inhibitors in Classical Hodgkin Lymphoma. Cancers (Basel). 2018 Jun 15;10(6).
Wu X, Li Y, Liu X, Cao S, Harrington SM, Chen C, et al. B7-H1(PD-L1) confers chemoresistance through ERK and p38 MAPK pathway in tumor cells. bioRxiv. 2018:308601.
Sproll KC, Balló H, Hoffmann TK, Scheckenbach K, Koldovsky U, Balz V, et al. Is there a role for the Fas-/Fas-Ligand pathway in chemoresistance of human squamous cell carcinomas of the head and neck (SCCHN)? Oral Oncology. 2009 2009/01/01/;45(1):69-84.
Zheng H, Liu Z, Liu T, Cai Y, Wang Y, Lin S, et al. Fas signaling promotes chemoresistance in gastrointestinal cancer by up-regulating P-glycoprotein. Oncotarget. 2014 Nov 15;5(21):10763-77.
Chappell DB, Restifo NP. T cell-tumor cell: a fatal interaction? Cancer Immunol Immunother. 1998;47(2):65-71.
Kim LH, Eow GI, Peh SC, Poppema S. The role of CD30, CD40 and CD95 in the regulation of proliferation and apoptosis in classical Hodgkin's lymphoma. Pathology. 2003 Oct;35(5):428-35.
Maggio EM, Van Den Berg A, de Jong D, Diepstra A, Poppema S. Low frequency of FAS mutations in Reed-Sternberg cells of Hodgkin's lymphoma. The Am J Pathol. 2003;162(1):29-35.
Article MetricsAbstract view : 47 times
PDF - 28 times
- There are currently no refbacks.
Copyright (c) 2022 Indonesian Journal of Cancer
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.