Extent and Location of Tumor-Infiltrating Lymphocytes in Microsatellite-Stable Colon Cancer Predict Outcome to Adjuvant Active Specific Immunotherapy

• Published in: Clinical cancer research Vol. 22; no. 2; pp. 346 - 356
• Main Authors: Turksma, Annelies W, Coupé, Veerle M H, Shamier, Marc C, Lam, Kevin L H, de Weger, Vincent A, Belien, Jeroen A M, van den Eertwegh, Alfons J, Meijer, Gerrit A, Meijer, Chris J L M, Hooijberg, Erik
• Format: Journal Article
• Language: English
• Published: United States 15.01.2016
• Subjects: Adult; Aged; Aged, 80 and over; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - pathology; Colonic Neoplasms - genetics; Colonic Neoplasms - immunology; Colonic Neoplasms - pathology; Colonic Neoplasms - therapy; Disease-Free Survival; Female; Humans; Immunotherapy, Active - methods; Lymphocytes, Tumor-Infiltrating - immunology; Lymphocytes, Tumor-Infiltrating - pathology; Male; Microsatellite Repeats - genetics; Middle Aged; Neoplasm Recurrence, Local - genetics; Neoplasm Recurrence, Local - immunology; Neoplasm Recurrence, Local - pathology; Neoplasm Recurrence, Local - therapy; Neoplasm Staging - methods; Prognosis
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.ccr-13-2462

To determine the prognostic and predictive value of tumor-infiltrating lymphocytes (TIL) in colon cancer in a cohort of patients who previously took part in a trial on adjuvant active specific immunotherapy (ASI). We determined the number and location of CD3 and CD8 positive T cells in archival tumor samples of 106 colon cancers. We correlated stromal and epithelial TIL numbers with tumor stage and treatment and determined the effects on disease-specific survival (DSS) and recurrence-free interval (RFI). On the basis of the data presented, we concluded that (i) high numbers of stromal CD3 T cells have positive prognostic value measured as DSS for patients with stage II microsatellite-stable tumors and (ii) high numbers of epithelial CD8-positive T cells have positive prognostic value measured as RFI for the group of patients with stage II microsatellite-stable tumors as well as for the whole group (so stage II plus stage III together). Furthermore, we concluded that high numbers of pre-existing stromal CD3-positive T cells are of positive predictive value in adjuvant ASI treatment measured as DSS as well as RFI. ASI therapy may contribute to an improved DSS and RFI in patients with microsatellite-stable colon tumors harboring high numbers of pre-existing stromal CD3(+) TIL. Validation in future clinical trials is awaited.