Abstract
Abstract Context: TIGIT has grown to be an increasingly important target for immunotherapy of cancer. However, it is unclear if there is an association between abundance of TIGIT expressing immune cells in tumor microenvironment and effectiveness of TIGIT-based intervention. This study utilizes an exploratory novel duplex immunohistochemical (IHC) assay to assess if the distribution patterns and/or the abundance of TIGIT-positive immune cells are related to the expression levels of TIGIT’s receptor PVR in tumor. Methods: Individual formalin-fixed, paraffin-embedded surgical resections and tissue microarray cores of 75 cervical, 84 esophageal, 79 non-small cell lung , and 81 small cell lung carcinoma specimens were stained using a duplex chromogenic IHC assay that detects PVR and TIGIT sequentially on a single slide. The slides were examined for (1) overall intensity and percentage of tumor staining positive for PVR, (2) percentage of tumor area occupied by TIGIT-expressing immune cells, and (3) distribution pattern of TIGIT-positive cells. For each specimen, overall PVR intensity was multiplied by percentage of tumor positive for PVR to generate the PVR Expression Score. Results: PVR and TIGIT staining at any intensity was widely observed in all four tumor types ranging from 91% to 100% of specimens positive for PVR and 77% to 100% of specimens positive for TIGIT. Little to no differences in the average percentages of PVR tumor positivity or TIGIT tumor area positivity were found among the four tumor types. However, individual tumor specimens differed widely in these two parameters. Among all 319 tumor specimens evaluated, the percentages of tumor expressing PVR at any intensity ranged from 0 to 100% with approximately 1/3 of the specimens having less than 50% and 3% showing no PVR expression. Percentages of tumor area occupied by TIGIT-positive cells ranged from 0% to 30% with approximately 40% of the specimens having less than 1%. Distribution patterns of TIGIT-expressing cells in each specimen was classified as peritumoral, intratumoral, or mixed. Specimens classified as peritumoral exhibited higher PVR Expression Scores than those classified as intratumoral. Specimens classified as having a mixed TIGIT-positive cell distribution pattern had an average PVR Expression Score that was intermediate between specimens having intratumoral and peritumoral TIGIT distribution patterns. Interestingly, no correlation was found between tumor PVR Expression Scores and abundance of TIGIT expressing cells in tumor area. Conclusion: The correlation between high tumor PVR expression levels and peritumoral distribution patterns of TIGIT-positive cells suggests PVR/TIGIT signaling pathway activation status could be important in infiltration of T cells into tumor parenchyma. Citation Format: Sara A. Moore, Julie Cheung, Aram B. Cholanians, June Clements, Jessica L. Baumann, Tsu-Shuen Tsao. Association between poliovirus receptor (PVR) expression in tumor and exclusion of immune cells expressing T cell immunoreceptor with Ig and ITIM domain (TIGIT) from tumor area [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6631.
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