The latest article from Nanjing University: CD8+ T cells in tumors require the presence of CXCR6 to exert their anti-tumor effects

The ultimate goal of tumor immunotherapy is to eliminate cancer cells, among which CD8+ cytotoxic T cells (CTL) are one of the key immune surveillance cells
.

The high abundance of CTLs with killing function in tumor tissues is a good prognostic indicator.

In 2019, Dr.
Lifei Hou of Harvard Medical School identified a group of pathogenic T cell subgroups with over-immune function in multiple sclerosis (MS) and mouse experimental encephalomyelitis (EAE) models that highly express CXCR6 1
.

Researchers at Nanjing University were inspired by the traditional Chinese idea of ​​yin and yang balance and used the phenotypic characteristics of highly activated inflammatory T cells in autoimmune diseases to speculate whether the phenotypic T cells in tumors are still highly activated or strongly cytotoxic Active tumor-killing ability? Under this assumption, the researchers explored the relationship between the expression of CXCR6 in the tumor microenvironment and tumor immunotherapy

The researchers first comprehensively analyzed the human and mouse colon cancer single-cell sequencing data published by Professor Zhang Zemin of Peking University and found that CXCR6 is only highly expressed in tumor tissues compared to peripheral tissues and secondary lymphoid tissues
.

The results were verified by immunofluorescence experiments and flow cytometry.

By comparing the expression changes of CXCR6 and CXCL16 before and after immunotherapy and the dynamic changes of CXCR6+CD8+ T cells and CXCL16 in peripheral blood and tumor tissues in tumor progression, it is found that CXCR6 is highly enriched in tumors and the ligand CXCL16 chemotaxis The effect is not the main cause, but is induced in the tumor tissue
.

CXCR6+CD8+ T cells induced by tumor tissue in vitro can not only inhibit tumor growth in mice, but also enhance the efficacy of anti-PD-1

It is worth mentioning that on August 2 this year, the Thorsten R Mempel research group of Massachusetts General Hospital's Center for Immunity and Inflammatory Diseases published an article in Cell that also pointed out that CXCR6 can help cytotoxic T lymphocytes in the tumor microenvironment.
In locating and receiving key survival signals, the expression of CXCR6 can predict the survival of a variety of immunogenic solid cancer patients 2
.

All in all, the study found that the presence of CXCR6 is required for cytotoxic T lymphocytes in tumors to exert anti-tumor effects.
This discovery will help the rational design of combined immunotherapy.
CXCR6 may be used as a detection indicator before adoptive transfer of CART cells.
, To provide a basis for the effectiveness of clinical transfer therapy
.

This result was titled CXCR6 Is Required for Anti-tumor Efficacy of Intratumoral CD8+ T Cell on August 30, 2021 in the Journal for ImmunoTherapy of Cancer (District 1, the official journal of the Society for Immunotherapy of Cancer under BMJ).
IF: 13.
751) published online ( https://doi.

Dr.
Wang Binglin from the School of Life Sciences of Nanjing University and Dr.
Wang Yi from Nanjing University of Traditional Chinese Medicine are the co-first authors of this paper.
Professors Sun Yang and Professor Xu Qiang from the School of Life Sciences and Deputy Chief Physician Chen Hongqi of Shanghai Sixth People’s Hospital are the co-authors of this paper.
Corresponding authors, Tian Zhigang, Academician of the School of Life Sciences, University of Science and Technology of China, Gu Yanhong, Director of the Oncology Department of Jiangsu Provincial People's Hospital, and Fan Zhimin, Director of the Anorectal Department of the Third Affiliated Hospital of Nanjing University of Chinese Medicine also contributed to the study
.

Edelweiss of the United States provided CXCR6 monoclonal antibody for this study.

 

references

1 Hou, L.

2 Di Pilato, M.