Targeting of CD40 and PD-L1 pathways inhibit progression of oral premalignant lesions in a carcinogen-induced model of oral squamous cell carcinoma.

p.aythelady61 shared this article with you from Inoreader Targeting of CD40 and PD-L1 pathways inhibit progression of oral premalignant lesions in a carcinogen-induced model of oral squamous cell carcinoma. Via Head and Neck Related Articles Targeting of CD40 and PD-L1 pathways inhibit progression of oral premalignant lesions in a carcinogen-induced model of oral squamous cell carcinoma. Cancer Prev Res (Phila). 2020 Dec 04;: Authors: Monteiro de Oliveira Novaes JA, Hirz T, Guijarro I, Nilsson M, Pisegna MA, Poteete A, Barsoumian HB, Fradette JJ, Chen LN, Gibbons DL, Tian X, Wang J, Myers JN, McArthur MJ, Bell D, William WN, Heymach JV Abstract We have previously demonstrated that PD-1 blockade decreased the incidence of high-grade dysplasia in a carcinogen induced murine model of OSCC. It remains unknown, however, whether there are additional factors involved in escape from immune surveillance that could serve as additional targets for immunoprevention. We performed the current study to further characterize the immune landscape of OPLs and determine the impact of targeting of the PD-1, CTLA-4, CD40, or OX40 pathways on the development of OPLs and oral carcinomas in the 4NQO model. The immune pathways were targeted using monoclonal antibodies or, in the case of the PD-1/PD-L1 pathway, using PD-L1 knockout mice. After intervention, tongues and cervical lymph nodes were harvested and analyzed for malignant progression and modulation of the immune milieu, respectively. Targeting of CD40 with an agonist monoclonal antibody was the most effective treatment to reduce transition of OPLs to OSCC; PD-1 alone or in combinatio n with CTLA-4 inhibition, or PD-L1 knockout, also reduced progression of OPL to OSCC albeit to a lesser extent. Distinct patterns of immune system modulation were observed for the CD40 agonists compared with blockade of the PD-1/PD-L1 axis with or without CTLA-4 blockade; CD40 agonist generated a lasting expansion of experienced/memory cytotoxic T-lymphocytes and M1 macrophages, whereas PD-1/CTLA-4 blockade resulted in a pronounced depletion of regulatory T-cells among other changes. These data suggest that distinct approaches may be used for targeting different steps in the development of OSCC, and that CD40 agonists merit investigation as a potential immunoprevention agents in this setting. PMID: 33277316 [PubMed - as supplied by publisher] View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.