Association of tumor-infiltrating T lymphocytes with intestinal-type gastric cancer molecular subtypes and outcome
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ORIGINAL ARTICLE
Association of tumor-infiltrating T lymphocytes with intestinal-type gastric cancer molecular subtypes and outcome Naziha Mansuri 1 & Eva-Maria Birkman 2 & Vanina D. Heuser 1 & Minnamaija Lintunen 2 & Annika Ålgars 3 & Jari Sundström 2 & Raija Ristamäki 3 & Laura Lehtinen 1 & Olli Carpén 1,4 Received: 15 May 2020 / Revised: 25 July 2020 / Accepted: 15 September 2020 # The Author(s) 2020
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-repairdeficient (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. Keywords Gastric cancer . Molecular subtypes . Tumor infiltration . Overall survival
Introduction Gastric cancer is the fifth most common cancer type globally, and the second most common cause of cancer death [1]. The common treatment modalities for gastric cancer patients
* Naziha Mansuri [email protected] 1
Research Center for Cancer, Infections and Immunity, Institute of Biomedicine, University of Turku, Kiinamyllynkatu, 10 20520 Turku, Finland
2
Department of Pathology, University of Turku and Turku University Hospital, Kiinamyllynkatu, 10 20520 Turku, Finland
3
Department of Oncology, Turku University Hospital, Kiinamyllynkatu 4-8, 20521 Turku, Finland
4
Medicum Research Program in Systems Oncology and HUSLAB, University of Helsinki and Helsinki University Hospital, Haartmaninkatu 3, 00014 Helsinki, Finland
include surgical resection and chemotherapy. Currently, the only targeted therapy is anti-HER2 treatment for cancers demonstrating HER2 amplifica
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