Lauren classification identifies distinct prognostic value and functional status of intratumoral CD8+T cells in gastric cancer

With dichotomous etiology and pathogenesis, intestinal type and diffuse type gastric cancers vary in their clinical and molecular features to the point of representing distinct entities. However, the differences of tumor-infiltrating immune cells within the two types of gastric cancer have not been well researched. This study was aimed to evaluate the functional impact of Lauren classification on immune contexture in gastric cancer patients. Tumor tissues of gastric cancer patients from Zhongshan Hospital and gastric cancer data from The Cancer Genome Atlas (TCGA) cohort were analyzed. By immunohistochemistry and flow cytometry, we found that intratumoral CD8(+)T cells were more abundant but less functional in diffuse type as compared with those in intestinal type tumor tissues. Survival analysis indicated that CD8(+)T cells yielded favorable prognosis only in intestinal type patients other than diffuse type cancer patients. Moreover, such diffuse type-associated CD8(+)T cell dysfunction was featured by elevated expression of immunosuppressive factors including interleukin-10 (IL-10), transforming growth factor-beta 1 (TGF-beta 1) and indoleamine 2,3-dioxygenase 1 (IDO1). In summary, we found that the density, prognostic significance and functional status of intratumoral CD8(+)T cells varied with Lauren subtypes in gastric cancer. These results further indicated Lauren classification might be a potential therapeutic marker, and should be considered in therapeutic decisions, especially immunotherapeutic eligibility.