CD8+ T-cell Density Is an Independent Predictor of Survival and Response to Adjuvant Chemotherapy in Stage III Colon Cancer

Abstract

We assessed CD8+ T-cell density in 351 resected stage II to III colon cancers from 2011 to 2015 and correlated the findings with disease-free survival and survival effect of adjuvant chemotherapy. Most tumors (70%) had high/intermediate CD8+ T-cell density, and this was significantly associated with mismatch repair deficiency compared with tumors with low CD8+ T-cell density (28% vs. 13%, P=0.003). Fewer tumors with high/intermediate CD8+ T-cell density had adverse histologic features compared with tumors with low CD8+ T-cell density including high tumor budding (16% vs. 27%) and venous (22% vs. 35%), lymphatic (54% vs. 65%), and perineural (23% vs. 33%) invasion (all with P<0.05). In the stage III cohort, high/intermediate CD8+ T-cell density was an independent predictor of disease-free survival on multivariate analysis (hazard ratio: 0.39, 0.21 to 0.71 95% CI, P=0.002). For stage III patients with high/intermediate CD8+ T-cell density, adjuvant chemotherapy was significantly associated with improved disease-free survival (hazard ratio: 0.28, 0.11 to 0.74 95% CI, P=0.01) whereas stage III patients with low CD8+ T-cell density did not have improved survival with adjuvant chemotherapy. In conclusion, in stage III colon cancer, CD8+ T-cell density is an independent prognostic biomarker for disease-free survival and may help to identify patients who benefit from adjuvant chemotherapy.

Spatial Effects of Infiltrating T cells on Neighbouring Cancer Cells and Prognosis in Stage III CRC patients

“…However, not all CD8 + T cells are equally effective in cell killing, due to exhaustion, high expression of checkpoint proteins in cancer cells, and both cell number and distribution within the tumour can affect patient outcomes. In a variety of tumour types, including, CRC, breast cancer, and non-small cell lung cancer, high numbers of infiltrating cytotoxic T cells are correlated with good prognosis [5][6][7][8][9][10][11][12]. The association between increased CD8 + T cell density and a favourable outcome, however, does not apply to all cancer types.…”

“…The tumour microenvironment is a complex milieu where interactions between cancer cells and the immune system play a pivotal role in shaping disease progression and therapy responses [4]. CD8 + or cytotoxic T cells are known for their antitumour immune response, releasing perforin and granzymes to create pores in the tumour cell plasma membrane and initiate cell death [5, 6]. However, not all CD8 + T cells are equally effective in cell killing, due to exhaustion, high expression of checkpoint proteins in cancer cells, and both cell number and distribution within the tumour can affect patient outcomes.…”