Total T Cell Density and Expression of T Memory Stem Cell Markers are Associated with Better Prognosis in Colon Cancer

Junli Ding; Hao Wang; Rui Hou; Yuxin Shi; Honghong Fan; Yuting Li; Jie Mei; Qinglin Zhang; Tingyan Ruan; Junying Xu

doi:10.2147/IJGM.S411122

Total T Cell Density and Expression of T Memory Stem Cell Markers are Associated with Better Prognosis in Colon Cancer

Int J Gen Med. 2023 Jun 5:16:2285-2294. doi: 10.2147/IJGM.S411122. eCollection 2023.

Authors

Junli Ding^#¹, Hao Wang^#¹, Rui Hou^#¹, Yuxin Shi¹, Honghong Fan¹, Yuting Li¹, Jie Mei¹, Qinglin Zhang², Tingyan Ruan¹, Junying Xu¹

Affiliations

¹ Department of Oncology, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi, 214023, People's Republic of China.
² Department of Gastroenterology, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi, 214023, People's Republic of China.

^# Contributed equally.

Abstract

Background: Immune checkpoint inhibitors have achieved limited clinical effectiveness in colon cancer. Stem memory T cells (TSCMs) and in-situ cytotoxic T cells are dominant contributors to host immunity. Currently, data on the correlation between TSCM and T cell abundance and clinicopathological characteristics in colon cancer are largely unavailable.

Methods: In-situ cytotoxic T cells are identified based on the quantification of CD3⁺ and CD8⁺ markers using immunohistochemistry (IHC) in the core of the tumor and the invasive margin of the tumor. The expression of representative markers of TSCMs, CD27 and CD95, was assayed using IHC in colon cancer tissues. Correlations between the levels of each marker and the clinicopathological characteristics as well as prognosis were evaluated.

Results: High densities of CD3⁺ and CD8⁺ T cells correlated with stage I-II tumors, whereas a lower infiltration of cytotoxic T cells correlated with advanced-stage tumors. CD27 and CD95 were both expressed in the membrane of T cells present in the tumor stroma and their levels showed a negative correlation with the TNM stage. CD3, CD8, and CD27 were expressed at the same locations simultaneously, indicating their coordinated action against cancer. In addition, cytotoxic T cell densities and CD27 and CD95 expression remained independent prognostic factors for overall survival.

Conclusion: In-situ cytotoxic T cells and TSCMs play important roles in colon cancer development. TSCMs marker CD27 and CD95 were both indicators of survival in patients with colon cancer. Thus, it is believed that TSCMs represent a desirable population for future use in combination immunotherapy.

Keywords: CD27; CD95; T cell; colon cancer; prognosis.

Grants and funding

This work was supported by the Wuxi Science and Technology Bureau Foundation (No. N20202018). Wuxi Municipal Health Commission Foundation (No. M202108), Beijing Hengji Health Management and Development Foundation (HJ-HX-ZLXD-202209-002), and Project of Wuxi Medical Center of Nanjing Medical University (WMCC202319).