Cardia cancer is different from non- cardia cancer in terms of local and systemic immune responses

Abstract

Introduction: This study sought to investigate the prognostic significance of tumor infiltrating lymphocytes (TILs) in respect to the prognostic nutritional index (PNI), neutrophil-to-lymphocyte ratio (NLR), and the topographic location of gastric tumors. Methods: Retrospective data from a prospectively maintained database of gastric cancer patients who underwent gastrectomy from January 2001 to December 2010 at a single center were retrieved. The distribution and prognostic significance of a subset of TILs using immunohistochemical staining for CD3, CD4, CD8, Foxp3, and granzyme B in 416 gastric cancer patients were evaluated. The PNI was calculated using preoperative laboratory values of 7781 gastric cancer patients. TILs and PNI were analyzed according to topographic location. Results: Gastric cancers in the cardia, compared to other locations, were associated with significantly lower CD8 and higher Foxp3 and granzyme B counts, without significant differences in PNI or NLR values. In cardia- localized cancer, multivariate analysis for clinicopathological and immunological factors revealed that lymph node metastasis and a high Foxp3/CD4 ratio were independent poor prognostic factors for overall survival. In non-cardia cancer, total gastrectomy, advanced T-classification, lymph node metastasis, low Foxp3, and low PNI were all poor prognostic factors. Conclusions: The distribution and prognostic impact of TILs and PNIs varied according to the longitudinal location of the cancer. Regulatory T lymphocytes were an unfavorable prognostic factor in cardia cancer and a favorable prognostic factor in non-cardia cancer.