A1 Refereed original research article in a scientific journal
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
Publisher: SPRINGER
Publication year: 2020
Journal: Virchows Archiv
Journal name in source: VIRCHOWS ARCHIV
Journal acronym: VIRCHOWS ARCH
Number of pages: 11
ISSN: 0945-6317
eISSN: 1432-2307
DOI: https://doi.org/10.1007/s00428-020-02932-3
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/50466302
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.
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