%0 Journal Article
%T Tissue-resident memory CD103+CD8+ T cells in colorectal cancer: its implication as a prognostic and predictive liver metastasis biomarker.
%A Liu S
%A Wang P
%A Wang P
%A Zhao Z
%A Zhang X
%A Pan Y
%A Pan J
%J Cancer Immunol Immunother
%V 73
%N 9
%D 2024 Jul 2
%M 38954030
%F 6.63
%R 10.1007/s00262-024-03709-2
%X BACKGROUND: Tissue-resident memory CD103+CD8+ T cells (CD103+CD8+ TRMs) are important components of anti-tumor immunity. However, the significance of CD103+CD8+ TRMs in colorectal cancer (CRC) and their advantages remain unclear.
METHODS: Clinical data and specimens were used to evaluate the significance of CD103+CD8+ TRMs in CRC. A mouse subcutaneous tumorigenesis model and colony-formation assay were conducted to evaluate the anti-tumor effects of CD103+CD8+ TRMs. Finally, the infiltration density and function of CD103+CD8+ TRMs in the tumors were evaluated using flow cytometry.
RESULTS: In this study, we showed that highly infiltrated CD103+CD8+ TRMs were associated with earlier clinical stage and negative VEGF expression in CRC patients and predicted a favorable prognosis for CRC/CRC liver metastases patients. Interestingly, we also found that CD103+CD8+ TRMs may have predictive potential for whether CRC develops liver metastasis in CRC. In addition, we found a positive correlation between the ratio of the number of α-SMA+ vessels to the sum of the number of α-SMA+ and CD31+ vessels in CRC, and the infiltration level of CD103+CD8+ TRMs. In addition, anti-angiogenic therapy promoted infiltration of CD103+CD8+ TRMs and enhanced their ability to secrete interferon (IFN)-γ, thus further improving the anti-tumor effect. Moreover, in vivo experiments showed that compared with peripheral blood CD8+ T cells, CD103+CD8+ TRMs infused back into the body could also further promote CD8+ T cells to infiltrate the tumor, and they had a stronger ability to secrete IFN-γ, which resulted in better anti-tumor effects.
CONCLUSIONS: We demonstrated that CD103+CD8+ TRMs have the potential for clinical applications and provide new ideas for combined anti-tumor therapeutic strategies, such as anti-tumor angiogenesis therapy and CAR-T combined immunotherapy.