Tackling molecular targets beyond PD-1/PD-L1: Novel approaches to boost patients' response to cancer immunotherapy. (March 2019)

• Record Type: Journal Article
• Authors: Omar, Hany A.; Tolba, Mai F.
• Is Part Of: Critical reviews in oncology/hematology. Volume 135(2019)
• Page Start: 21
• Page End: 29
• Publication Date: 2019-03
• Subjects: PD-1 programmed death-1 receptor -- PD-L1 programmed death-1 ligand -- CTLA-4 cytotoxic T-lymphocyte associated protein-4 -- ICOS T-cell inducible co-stimulator -- VISTA V-domain Ig suppressor of T-cell activation -- CDK12 cyclin-dependent kinase 12 -- EZH2 enhancer of Zeste homolog 2 -- TLRs toll-like receptors -- TNF tumor necrosis factor -- GITR glucocorticoid-induced TNF receptor -- αCD40 agonistic CD40 mAb -- MTD maximal tolerated dose -- NSCLC non-small cell lung cancer -- NHL non-Hodgkin's lymphoma -- SCLC small cell lung cancer -- TNBC triple negative breast cancer -- BCG Bacillus Calmette-Guerin -- TAA tumor-associated antigen; Immunotherapy -- ICOS -- CD40 -- CD47 -- VISTA -- CDK12 -- EZH2 -- TLRs -- OX40; Oncology -- Periodicals; Hematology -- Periodicals; 616.994
• DOI: 10.1016/j.critrevonc.2019.01.009
• Languages: English
• ISSNs: 1040-8428

Abstract

Abstract: In the new era of immunotherapy, which has changed the clinical oncology practice guidelines, there is a pressing need for finding novel approaches to tune up the clinical outcomes of immunotherapy and extend its benefits to a wider cohort of cancer patients. Several non-classical molecular immune targets beyond PD-1/PD-L1 signaling were shown to be engaged as feedback resistance circuits to shut down the antitumor immune response mediated by the classical immune checkpoint inhibitors. Those include T-cell inducible co-stimulator (ICOS), CD40, CD47, V-domain Ig suppressor of T-cell activation (VISTA), cyclin-dependent kinase (CDK)12, enhancer of Zeste homolog 2 (EZH2), toll-like receptors (TLRs) and OX-40 (CD134). Herein we critically discussed the latest studies concerned with understanding the mechanisms involved in the negative clinical response to classical immunotherapies and strategies to optimize the efficacy of cancer immunotherapy through novel combinatorial approaches.