Abstract 6633: T regulatory cell subsets in colorectal cancer: friends or foes

Abstract T cells in the tumor microenvironment (TME) have diverse roles in anti-tumor immunity. Different T cell subsets may have opposing roles in tumor progression, especially in inflammatory cancers such as colorectal cancer (CRC). In different series of studies, we performed extensive characterization and critical analyses of T regulatory cell (Treg)-related markers and key inhibitory immune checkpoints (ICs) in CD4+ and CD8+ T cell subsets in the TME and periphery of CRC patients. We found a significant increase in levels of CD4+FoxP3+Helios+ T cells, which represent potentially highly immunosuppressive Tregs, in the TME. Additionally, tumor-infiltrating CD4+ T cells upregulated PD-1, CTLA-4, TIM-3 and LAG-3 immune checkpoints. CTLA-4, TIM-3, and LAG-3 were mainly co-expressed on FoxP3+Helios+ Tregs in the TME. Additionally, we found that FoxP3 expression and ICs including PD-1, CTLA-4, TIM-3, and LAG-3 were significantly upregulated in tumor-infiltrating CD8+ T cells. We then investigated associations between different tumor-infiltrating CD4+ and CD8+ T cell subpopulations and disease-free survival (DFS). Interestingly, a high frequency of circulating CD4+FoxP3+ Tregs was associated with poorer DFS, while higher frequency of these cells in the TME was associated with better DFS. Additionally, high frequencies of circulating CD4+FoxP3+Helios+ Tregs and tumor-infiltrating CD4+FoxP3-Helios- T cells were associated with poorer DFS. Moreover, a high frequency of CD4+FoxP3+Helios-PD-1+ Tregs in circulation was associated with worse DFS. In contrast, high frequencies of CD4+TIM-3+ T cells, FoxP3+Helios+TIM-3+ Tregs, and FoxP3-Helios+TIM-3+ CD4+ T cells in circulation were associated with longer DFS. Additionally, we found that high levels of certain circulating CD8+ T cell subsets (TIM-3+, FoxP3-Helios-TIM-3+ and FoxP3-Helios+TIM-3+ cells) were associated with longer DFS. In the TME, elevated levels of CD25+ and TIM-3+ CD8+ T cells, and FoxP3+Helios-TIM-3+ CD8+ Tregs were associated with better DFS. These data show that circulating and tumor-infiltrating immune checkpoint-expressing CD4+ and CD8+ Treg/T cell subsets play different roles in disease prognoses, and certain subsets could serve as independent predictive biomarkers in CRC patients. Citation Format: Eyad Elkord. T regulatory cell subsets in colorectal cancer: friends or foes [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 6633.