TY - JOUR
T1 - Tumor infiltration of inactive CD8 + T cells was associated with poor prognosis in Gastric Cancer
AU - Katayama, Naoki
AU - Ohuchida, Kenoki
AU - Son, Kiwa
AU - Tsutsumi, Chikanori
AU - Mochida, Yuki
AU - Noguchi, Shoko
AU - Iwamoto, Chika
AU - Torata, Nobuhiro
AU - Horioka, Kohei
AU - Shindo, Koji
AU - Mizuuchi, Yusuke
AU - Ikenaga, Naoki
AU - Nakata, Kohei
AU - Oda, Yoshinao
AU - Nakamura, Masafumi
N1 - Publisher Copyright:
© The Author(s) 2024.
PY - 2025/3
Y1 - 2025/3
N2 - Background: Gastric cancer (GC) shows limited response to immune checkpoint inhibitors due to its complex tumor immune microenvironment (TIME). This study explores the functions of various immune cells in the complex TIME in GC. Methods: We assessed CD8 + T-cell infiltration of GC tissues by immunohistochemistry, and performed single-cell RNA sequencing (scRNA-seq) of tumor and normal tissues from 34 patients with GC. Results: We categorized 157 GC patients into LOW, MID, and HIGH groups based on their CD8 + T-cell infiltration. Overall survival was notably lower for the HIGH and LOW groups compared with the MID group. Our scRNA-seq data analysis showed that CD8 + T-cell activity markers in the HIGH group were expressed at lower levels than in normal tissue, but the T-cell-attracting chemokine CCL5 was expressed at a higher level. Notably, CD8 + T-cells in the HIGH group displayed lower PD1 expression and higher CTLA4 expression. TCR repertoire analysis using only Epstein–Barr virus-negative cases showed that CD8 + T-cell receptor clonality was lower in the HIGH group than in the MID group. Furthermore, in the HIGH group, the antigen-presenting capacity of type 1 conventional dendritic cells was lower, the immunosuppressive capacity of myeloid-derived suppressor cells was higher, and the expression of CTLA4 in regulatory T-cells was higher. Conclusion: The present data suggest that the infiltration of inactive CD8 + T-cells with low clonality is induced by chemotaxis in the HIGH group, possibly leading to a poor prognosis for patients with GC.
AB - Background: Gastric cancer (GC) shows limited response to immune checkpoint inhibitors due to its complex tumor immune microenvironment (TIME). This study explores the functions of various immune cells in the complex TIME in GC. Methods: We assessed CD8 + T-cell infiltration of GC tissues by immunohistochemistry, and performed single-cell RNA sequencing (scRNA-seq) of tumor and normal tissues from 34 patients with GC. Results: We categorized 157 GC patients into LOW, MID, and HIGH groups based on their CD8 + T-cell infiltration. Overall survival was notably lower for the HIGH and LOW groups compared with the MID group. Our scRNA-seq data analysis showed that CD8 + T-cell activity markers in the HIGH group were expressed at lower levels than in normal tissue, but the T-cell-attracting chemokine CCL5 was expressed at a higher level. Notably, CD8 + T-cells in the HIGH group displayed lower PD1 expression and higher CTLA4 expression. TCR repertoire analysis using only Epstein–Barr virus-negative cases showed that CD8 + T-cell receptor clonality was lower in the HIGH group than in the MID group. Furthermore, in the HIGH group, the antigen-presenting capacity of type 1 conventional dendritic cells was lower, the immunosuppressive capacity of myeloid-derived suppressor cells was higher, and the expression of CTLA4 in regulatory T-cells was higher. Conclusion: The present data suggest that the infiltration of inactive CD8 + T-cells with low clonality is induced by chemotaxis in the HIGH group, possibly leading to a poor prognosis for patients with GC.
KW - CD8-positive T-cells
KW - Gastric cancer
KW - Immunosuppressive cell
KW - Interferon gamma
KW - Tumor-infiltrating lymphocytes
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U2 - 10.1007/s10120-024-01577-4
DO - 10.1007/s10120-024-01577-4
M3 - Article
C2 - 39722065
AN - SCOPUS:85212983106
SN - 1436-3291
VL - 28
SP - 211
EP - 227
JO - Gastric Cancer
JF - Gastric Cancer
IS - 2
ER -