Viral-induced Modulation of Multiple Checkpoint Proteins in Cancers.

TitleViral-induced Modulation of Multiple Checkpoint Proteins in Cancers.
Publication TypeJournal Article
Year of Publication2017
AuthorsNuovo GJ, Folcik VA, Magro C
JournalAppl Immunohistochem Mol Morphol
Volume25
Issue6
Pagination407-414
Date Published2017 07
ISSN1533-4058
KeywordsCell Cycle Proteins, Humans, Neoplasms, Papillomaviridae
Abstract

Therapy with checkpoint inhibitors represents a major advance in cancer treatment. The purpose of this study was to examine the expression patterns of the checkpoint proteins programmed death ligand 1 (PD L1), PD L2, indoleamine 2,3-dioxygenase 1 (IDO1), and cytotoxic T-lymphocyte antigen 4 (CTLA4) in cancers including those associated with viral infections. Normal, noninflamed tissues rarely express checkpoint proteins with exceptions including the placenta and stomach. Expression of PD L1 was noted in 30%, PD L2 in 18%, IDO1 in 13%, and CTLA4 in 14% of 333 nonviral malignancies including endometrial, ovarian, lung, and breast cancers. The expression of each checkpoint protein was significantly higher among 166 cases of viral-related (mostly human papillomavirus) cancers where expression of PD L1 was noted in 84%, PD L2 in 67%, IDO1 in 61%, and CTLA4 in 37% (each P value <0.001); 97% of the viral-related cancers showed expression of at least 1 checkpoint protein. In addition, over 90% of the CD8 cells in the viral-associated cancers were quiescent based on low coexpression of Ki-67 as well as pSTAT1. It is concluded that viral infection in cancers is associated with the increased expression of key checkpoint proteins. This indicates that cancers with productive viral infection may be better targets for checkpoint inhibitor therapy.

DOI10.1097/PAI.0000000000000429
Alternate JournalAppl Immunohistochem Mol Morphol
PubMed ID28697066
Related Faculty: 
Cynthia M. Magro, M.D.

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