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- Title
Association of tumor-infiltrating T lymphocytes with intestinal-type gastric cancer molecular subtypes and outcome.
- Authors
Mansuri, Naziha; Birkman, Eva-Maria; Heuser, Vanina D.; Lintunen, Minnamaija; Ålgars, Annika; Sundström, Jari; Ristamäki, Raija; Lehtinen, Laura; Carpén, Olli
- 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.
- Subjects
T cells; STOMACH cancer; PROGNOSIS; FACTOR analysis; INTESTINES; LYMPHOCYTE count
- Publication
Virchows Archiv: European Journal of Pathology, 2021, Vol 478, Issue 4, p707
- ISSN
0945-6317
- Publication type
Article
- DOI
10.1007/s00428-020-02932-3