Work

Interferon-γ derived from exhausted T cells contributes to both maintaining exhaustion within the tumor microenvironment and the memory recall response 3318

Year: 2025

Type: article

Abstract: Description Exhausted T cells (TEX) have traditionally been considered dysfunctional defined by impaired production of cytotoxic cytokines. However, recent studies have provided evidence that these cells may not be fully dysfunctional and retain the ability to produce interferon-γ (IFNγ). To investigate how IFNγ derived from those TEX modulate the tumor microenvironment (TME), we established a tamoxifen inducible murine model controlled under LAG3 expression, a hallmark inhibitory receptor expressed on exhausted cells, which allows for assessing impacts of a temporal genetic deletion of Ifng from TEX (Lag3iCreERT2IfngL/LRosa26LSLtdTomato). Assessing the transcriptional profile of IFNγ shows that IFNγ+ CD8+ T cells are restricted to the TME, marked by enhanced inhibitory receptor expression. Our Lag3iCreERT2IfngL/LRosa26LSLtdTomato model illustrates that IFNγ ablation in TEX inhibits intratumoral TEX expansion and impairs host memory response in vivo upon tumor re-challenge. In summary, by utilizing novel murine models, this study highlights the functional capacity of IFNγ+ TEX in the tumor immunity and their potential to be reinvigorated as therapeutic targets for cancer. Funding Sources P01 AI108545 Topic Categories Tumor Immunology: Cellular Responses and Tumor Microevironment (TIME)

Source: The Journal of Immunology

DOI: 10.1093/jimmun/vkaf283.1134

Authors: Yingtong Dou, Vaishali Aggarwal, Creg Workman, Dario Angelo Alberto Vignali

Institutions: University of Pittsburgh, UPMC Health System, University of Pittsburgh Medical Center

Language: English

Topic: Cancer Immunotherapy and Biomarkers

Subfield: Oncology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: bronze

OpenAlex ID: W4416446481