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Viral-induced Modulation of Multiple Checkpoint Proteins in Cancers
Gerard J Nuovo1, Virginia A Folcik, Cynthia Magro
1*Phylogeny Inc., Powell †The Ohio State University Comprehensive Cancer Center ‡The Ohio State University Department of Computer Science & Engineering, Columbus, OH §Cornell Medical Center, New York, NY.
Viral infections significantly increase checkpoint protein expression in cancers, including PD L1 and IDO1. This suggests viral-associated cancers may respond better to checkpoint inhibitor therapies.
Area of Science:
- Oncology
- Immunology
- Virology
Background:
- Checkpoint inhibitors are a significant advancement in cancer therapy.
- Understanding checkpoint protein expression is crucial for optimizing treatment strategies.
Purpose of the Study:
- To investigate the expression patterns of programmed death ligand 1 (PD L1), PD L2, indoleamine 2,3-dioxygenase 1 (IDO1), and cytotoxic T-lymphocyte antigen 4 (CTLA4).
- To compare expression in nonviral malignancies versus virally associated cancers.
Main Methods:
- Analysis of checkpoint protein expression in 333 nonviral and 166 viral-associated cancer cases.
- Assessment of CD8 cell quiescence using Ki-67 and pSTAT1 coexpression.
Main Results:
- Checkpoint proteins were rarely expressed in normal tissues.
- Significantly higher expression of PD L1, PD L2, IDO1, and CTLA4 was observed in viral-related cancers (p < 0.001).
- 97% of viral-related cancers expressed at least one checkpoint protein, with over 90% of CD8 cells quiescent.
Conclusions:
- Viral infections are associated with increased expression of key cancer checkpoint proteins.
- Cancers with active viral infections may be more responsive to checkpoint inhibitor therapy.
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