Bystander CD4+ T cells infiltrate human tumors and are phenotypically distinct. (31st December 2022)

• Record Type: Journal Article
• Authors: Li, Shamin; Zhuang, Summer; Heit, Antja; Koo, Si-Lin; Tan, Aaron C.; Chow, I-Ting; Kwok, William W.; Tan, Iain Beehuat; Tan, Daniel S.W.; Simoni, Yannick; Newell, Evan W.
• Is Part Of: Oncoimmunology. Volume 11:Number 1(2022)
• Publication Date: 2022-12-31
• Subjects: CD4 -- CD8 -- CD39 -- TIL -- HCMV -- cancer -- tumor -- infiltrating -- bystander; Tumors -- Immunological aspects -- Periodicals; Neoplasms -- therapy -- Periodicals; Immunotherapy -- Periodicals; 616.994
• DOI: 10.1080/2162402X.2021.2012961
• Languages: English
• ISSNs: 2162-402X

Abstract

ABSTRACT: Tumor-specific T cells likely underpin effective immune checkpoint-blockade therapies. Yet, most studies focus on Treg cells and CD8 + tumor-infiltrating lymphocytes (TILs). Here, we study CD4 + TILs in human lung and colorectal cancers and observe that non-Treg CD4 + TILs average more than 70% of total CD4 + TILs in both cancer types. Leveraging high dimensional analyses including mass cytometry, we reveal that CD4 + TILs are phenotypically heterogeneous, within each tumor and across patients. Consistently, we find different subsets of CD4 + TILs showing characteristics of effectors, tissue resident memory (Trm) or exhausted cells (expressing PD-1, CTLA-4 and CD39). In both cancer types, the frequencies of CD39 – non-Treg CD4 + TILs strongly correlate with frequencies of CD39 – CD8 + TILs, which we and others have previously shown to be enriched for cells specific for cancer-unrelated antigens (bystanders). Ex-vivo, we demonstrate that CD39 – CD4 + TILs can be specific for cancer-unrelated antigens, such as HCMV epitopes. Overall, our findings highlight that CD4 + TILs can also recognize cancer-unrelated antigens and suggest measuring CD39 expression as a straightforward way to quantify or isolate bystander CD4 + T cells.