Association of tumor-infiltrating T lymphocytes with intestinal-type gastric cancer molecular subtypes and outcome

Abstract

While host immune response is likely to be important for the prognosis of gastric cancer patients, detailed information on the T lymphocyte infiltration in different gastric cancer subtypes is lacking. Here, we studied the presence of CD3, CD8, and FOXP3 (Forkhead box p3) expressing T lymphocytes in a retrospective cohort of 190 intestinal gastric and gastroesophageal adenocarcinomas. The cancers represented four distinct molecular subtypes: Epstein-Barr virus–positive (EBV+), mismatch-repair-deficient (MMR-D), aberrant TP53, and the “other” subtype. The absolute numbers of CD3+, CD8+, and FOXP3+ T lymphocytes were analyzed in relation with these molecular subtypes and selected clinicopathological parameters. Overall, there was a large variation in the amount of infiltrating T lymphocyte in all molecular subtypes. Among the subtypes, EBV+ cancers differed from the other subtypes in increased lymphocyte infiltration and high CD8+/FOXP3+ ratio. While the TP53 aberrant subtype did not differ in the absolute amount of T lymphocyte, the ratio of CD8+/FOXP3+ and CD3+/FOXP3+ cells was highest in this subtype, possibly reflecting immunosuppression associated with genomic instability. Increased CD3+ and CD8+ T lymphocyte infiltrates were associated with better survival, and remained as independent prognostic factors in a multivariate analysis. This study is the first to investigate lymphocytic infiltration within four molecular subtypes of intestinal-type gastric cancer in a European cohort. The results provide an important addition to the current knowledge of T lymphocyte–dependent immune response in gastric cancer and its prognostic significance.

Progression on the Roles and Mechanisms of Tumor-Infiltrating T Lymphocytes in Patients With Hepatocellular Carcinoma

“…Now, there's no reliable biomarker for distinguishing nTregs from iTregs. In recent years, Foxp3+ T cells have been found in many tumors, such as HCC (17), pancreatic ductal adenocarc (18), colorectal cancer (19), gastric cancer (20), and esophageal cancer (21), suggesting that Foxp3+ T cells participated in the tumor progression. However, the subsets of infiltrating Foxp3+ T cells in tumors remained unclear.…”

FHOD1 and FMNL1 formin proteins in intestinal gastric cancer: correlation with tumor-infiltrating T lymphocytes and molecular subtypes

“…Indeed, we found a correlation between tumor cell FHOD1 expression and high numbers of CD8 + lymphocytes. TP53-mutated GC tumors generally display lower intratumoral lymphocyte infiltration and wildtype TP53 tumors, in turn, harbor high numbers of infiltrating lymphocytes [24]. We found down-regulation of FHOD1 in TP53 aberrant tumors and upregulation of FHOD1 in tumors with high lymphocyte infiltration.…”

“…In our previous study, we stained immune cell markers CD3, CD8 and FOXP3 from the same ngTMA utilized in this study, and saw that high intratumoral infiltration with CD3-and CD8-positive lymphocytes was significantly associated with better outcome [24]. To find out whether there was any association of FHOD1 or FMNL1 expression with intratumoral lymphocyte infiltration in these TMA samples, we tested the correlation between FHOD1 and FMNL1 expression and the number of CD3-, CD8and FOXP3-positive lymphocytes in individual samples.…”

“…Our previous study with the same GC cohort showed that increased numbers of intratumoral CD3 + and CD8 + T lymphocytes were associated with a favorable outcome [24]. Here, we wanted to investigate whether intratumoral T lymphocyte infiltration and formin expression in the same tissue samples are interconnected.…”

Study Of The Association Of Tumor Deposits With Tumour-infiltrating Lymphocytes And Prognosis In Gastric Cancer Patients

“…Previous studies have found that TDs are present not only in colorectal cancer but also in other solid malignancies, such as gastric, bile duct, and pancreatic cancers [2,16]. Currently, although a few studies have shown that the presence of TDs is an independent prognostic factor for a poor prognosis in gastric cancer [9,10], the mechanism of TDs formation is unclear.For colorectal cancer, the importance of TDs has been recognized and has been included in category N in the 7th edition of the TNM staging system for colorectal cancer. However, in the 8th edition of the TNM staging system, TDs are considered as a metastatic lymph node in gastric cancer, which is contrary to the ndings of the current study.…”