Intratumoral CD103+CD4+ T cell infiltration defines immunoevasive contexture and poor clinical outcomes in gastric cancer patients
Yun Gu,Yifan Chen,Kaifeng Jin,Yifan Cao,Xin Liu,Kunpeng Lv,Xudong He,Chao Lin,Hao Liu,He Li,Hongyong He,Jing Qin,Ruochen Li,Heng Zhang,Weijuan Zhang +14 more
TL;DR: This study revealed that intratumoral CD103+CD4+T cell infiltration defined immunoevasive contexture and predicted poor prognosis and inferior responsiveness to fluorouracil-based ACT, and recommended that CD103-CD4- T cells might be a potential immunotherapeutic target for gastric cancer.
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Abstract: Our previous study has identified intratumoral CD103+CD8+ T cells as a favorable prognostic factor in gastric cancer. However, the significance of CD103+CD4+ T cells in gastric cancer hasn't yet been elucidated. Here, we aimed to investigate the clinical significance and phenotype characteristics of intratumoral CD103+CD4+ T cells in gastric cancer. In our study, 469 formalin-fixed and paraffin-embedded samples and 24 fresh tissue specimens of patients with gastric cancer from Zhongshan Hospital were included. We manifested that intratumoral CD103+CD4+ T cells in gastric cancer predicted poor overall survival and inferior responsiveness to fluorouracil-based ACT. The density and phenotypic characteristics of CD103+CD4+ T cells in gastric cancer were detected by immunohistochemistry and flow cytometry, which showed that CD103+CD4+ T cells exhibited an immunosuppressive phenotype and higher retention capacity in tumor tissues. Furthermore, increased CD103+CD4+ T cells contributed to CD8+T cell dysfunction with decreased granzyme B (GZMB), interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α) and perforin (PRF-1) expression in gastric cancer. Overall, this study revealed that intratumoral CD103+CD4+T cell infiltration defined immunoevasive contexture and predicted poor prognosis and inferior responsiveness to fluorouracil-based ACT. Therefore, we recommended that CD103+CD4+ T cells might be a potential immunotherapeutic target for gastric cancer.
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Identification and validation of an immunogenic subtype of gastric cancer with abundant intratumoural CD103+CD8+ T cells conferring favourable prognosis.
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TL;DR: In vitro analysis showed that CD103+CD8+ T cells were more functionally restored after PD-1 blockade than CD103-CD8- T cells, and efforts to increase intratumoural T cell frequency might be a novel therapeutic strategy in gastric cancer.
Gastric cancer progression associated with local humoral immune responses
López-Vidal Yolanda,Ponce-de-León Sergio,Esquivel-Solís Hugo,Amieva-Fernández Rosa Isabel,Barreto-Zúñiga Rafael,Torre-Delgadillo Aldo,Castillo-Rojas Gonzalo +6 more
TL;DR: Gastric cancer is characterized by progressive accumulation of a concentrated, specific IgA response against H. pylori, beginning with an abnormal increase in the entire stomach but particularly in the adjacent non-tumor tissue, and it is possible that this strong immune response also participates in some degree in the damage and in the development of gastric cancer to some extent.