SUNGKYUNKWAN UNIVERSITY SCHOOL OF MEDICINE

In a collaborative study with Rafi Ahmed and Suresh S. Ramalingam of Emory University in Georgia, U.S.A., Prof. Se Jin Lim (Department of Medicine, Division of Immunology, Basic Medicine) and colleagues have identified a population of TCF1-expressing CD8 T cells with exclusive proliferative capacity within the tumor microenvironment, and they are predominantly located in tertiary lymphoid structures.

 CD8 T cells are the primary cells responsible for antitumor immunity within the tumor microenvironment. In this study, using several mouse tumor models and human lung cancer samples, we found that tumor-specific CD8 T cells consist of a progenitor cell population expressing the transcriptional regulator TCF1 and an effector cell population expressing Tim-3. We found that TCF1-expressing CD8 T cells have no cytolytic capacity but have the ability to proliferate exclusively after antigen stimulation, and that they continue to maintain tumor-specific CD8 T cell responses as they differentiate into Tim-3-expressing effector T cells with cytolytic capacity.

Furthermore, using human lung cancer samples, we analyzed the location of CD8 T cell populations in the tumor microenvironment and found that Tim-3-expressing effector T cells infiltrate into the tumor and interact with tumor cells, whereas TCF1-expressing progenitor T cells remain distant from tumor cells as they are predominantly located in tertiary lymphoid structures.

Furthermore, by comparing the proliferation of CD8 T cells in mouse tumor models and human lung cancer patients, the researchers found that CD8 T cells in mouse tumor models are mostly actively proliferating, whereas CD8 T cells in human lung cancer patients are mostly quiescent and only a few Tim-3-expressing effector T cells are proliferating, and that this difference is due to the difference in the post-tumor period between the models.

"The predominant location of TCF1-expressing CD8 T cells in the tertiary lymphoid structures that induce therapeutic responsiveness to PD-1 immune checkpoint inhibitors suggests that there may be important mechanisms for maintaining this cell population, and look forward to further studies. This study may also help us better understand the differences between the results obtained in mouse tumor models and cancer patients."

The research was supported by the National Research Foundation of Korea and the National Cancer Centers Public Interest Cancer Research Program and was published Oct. 10 in the Proceedings of the National Academy of Sciences (PNAS, IF: 12.779).

Location of TCF1-expressing progenitor cell populations in tumor tissue from patients with non-small cell lung cancer. 

(Source: Im and Obeng et al. (2023) PNAS)

Title: Characteristics and anatomic location of PD-1+TCF1+ stem-like CD8 T cells in chronic viral infection and cancer

Author: Se jin Lim (Corresponding author)