Abstract 4970: Prognostic role of CD112R, PD-1 and Ki67 expression in CD8+cytotoxic T cells in colorectal cancer

Abstract

Abstract Expression of inhibitory immune checkpoint receptors such as CD112R (Poliovirus Receptor-Related Immunoglobulin Domain-Containing Protein, PVRIG) and PD-1 on CD8+ lymphocytes are considered to indicate an “exhausted” stage of T cell activation while Ki67 protein expression in these cells is viewed as sign of activity or expansion. To assess the prognostic impact of the clinical impact of CD112R, PD-1, and Ki67 expression of CD8+ lymphocytes, expression of these proteins was analyzed by fluorescent multiplex immunohistochemistry on a tissue microarray containing 384 colorectal cancers with clinical follow-up data. An elevated fraction of CD8+Ki67+ cells was linked to the absence of nodal metastasis and longer survival in these tumors (p≤0.0039 each). CD112R and PD-1 expression was detected at variable intensity levels and were separately quantitated in both ki67+ (expanding) and Ki67 negative (non-expanding) CD8+ cytotoxic lymphocytes. Elevated PD-1 expression in CD8+ T cells was associated with an absence of nodal metastasis (p=0.004) and longer overall survival in all CD8+ cells (p=0.005). This association was more evident in the subset of expanding (p<0.0001) than in non-expanding (p=0.034) cytotoxic T cells. Elevated CD112R expression level in CD8+ T cells were linked to a low tumor grade (p=0.048), absence of nodal metastasis (p=0.023) and a prolonged overall survival (p=0.041) but these associations were not retained in subgroups of either expanding or non-expanding CD8+ cells. Patients with an elevated fraction of CD8+ki67+CD112R+PD-1+cells exhibited a particularly good prognosis. In conclusion, our data reveal that “exhausted” CD112R+/ PD-1+CD8+ cytotoxic T lymphocytes are able to expand (ki67+). This observation in combination with the good prognosis of cancers with high number of expanding exhausted cells argues for retained cytotoxic activity of CD112R+/ PD-1+ CD8+ T lymphocytes. Citation Format: Ronald Simon, Niclas Christian Blessin, Tim Mandelkow, Elena Bady, Claudia Hube-Magg, Guido Sauter, Maximilian Lennartz, Christoph Fraune, Sören A. Weidemann, Katharina Möller, Franziska Büscheck. Prognostic role of CD112R, PD-1 and Ki67 expression in CD8+cytotoxic T cells in colorectal cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4970.