Yu Zhang1,2, Zhen-Xiong Zhao1,2, Jian-Peng Gao1,2, Ya-Kai Huang1,2, Hua Huang3,4. 1. Department of Gastric Surgery, Fudan University Shanghai Cancer Center, 270 Dongan Road, Shanghai, 200032, People's Republic of China. 2. Department of Oncology, Shanghai Medical College, Fudan University, 270 Dongan Road, Shanghai, 200032, People's Republic of China. 3. Department of Gastric Surgery, Fudan University Shanghai Cancer Center, 270 Dongan Road, Shanghai, 200032, People's Republic of China. huahuangvip@sina.com. 4. Department of Oncology, Shanghai Medical College, Fudan University, 270 Dongan Road, Shanghai, 200032, People's Republic of China. huahuangvip@sina.com.
Abstract
PURPOSE: Defining the phenotypic characteristics of CD8+ T cell subsets in gastric cancer (GC) can help remodel the immune microenvironment of the tumor, thereby improving patient prognosis. CD226 has recently been shown to regulate the activity of CD8+ T cell in several malignancies. However, the clinical relevance of CD226+CD8+ T cells in GC remains unclear. METHODS: Fudan University Shanghai Cancer Center (FUSCC) cohort (n = 316), The Cancer Genome Atlas (TCGA) cohort (n = 407), KUGH/KUCM cohort (n = 202), and Asian Cancer Research Group (ACRG) cohort (n = 300) were included in prognosis and response to adjuvant chemotherapy (ACT) analyses. Flow cytometry and multiplex immunostaining were used to characterize CD226+CD8+ T cells. RESULTS: CD226+CD8+ T cells predicted favorable outcomes in patients undergoing curative resection for GC. GC patients with high CD226+CD8+ T cell infiltration benefitted more from adjuvant chemotherapy. CD155 is upregulated in GC tissues and is associated with decreased intra-tumoral CD226+CD8+ T cell infiltration. The combination of intra-tumoral CD226+CD8+ T cells and CD155 is a strong prognostic predictor in patients with GC. CONCLUSION: CD226+CD8+ T cells may represent a novel therapeutic target and a useful marker of prognosis and therapeutic response in patients with GC.
PURPOSE: Defining the phenotypic characteristics of CD8+ T cell subsets in gastric cancer (GC) can help remodel the immune microenvironment of the tumor, thereby improving patient prognosis. CD226 has recently been shown to regulate the activity of CD8+ T cell in several malignancies. However, the clinical relevance of CD226+CD8+ T cells in GC remains unclear. METHODS: Fudan University Shanghai Cancer Center (FUSCC) cohort (n = 316), The Cancer Genome Atlas (TCGA) cohort (n = 407), KUGH/KUCM cohort (n = 202), and Asian Cancer Research Group (ACRG) cohort (n = 300) were included in prognosis and response to adjuvant chemotherapy (ACT) analyses. Flow cytometry and multiplex immunostaining were used to characterize CD226+CD8+ T cells. RESULTS: CD226+CD8+ T cells predicted favorable outcomes in patients undergoing curative resection for GC. GC patients with high CD226+CD8+ T cell infiltration benefitted more from adjuvant chemotherapy. CD155 is upregulated in GC tissues and is associated with decreased intra-tumoral CD226+CD8+ T cell infiltration. The combination of intra-tumoral CD226+CD8+ T cells and CD155 is a strong prognostic predictor in patients with GC. CONCLUSION: CD226+CD8+ T cells may represent a novel therapeutic target and a useful marker of prognosis and therapeutic response in patients with GC.
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