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The prognostic value of CD3+ tumor-infiltrating lymphocytes for stage II colon cancer according to use of adjuvant chemotherapy: A large single-institution cohort study
Authors:Edoardo Francini  Fang-Shu Ou  Stefano Lazzi  Roberto Petrioli  Andrea G Multari  Guido Pesola  Luciana Messuti  Elena Colombo  Virginia Livellara  Serena Bazzurri  Sara Cherri  Salvatora T Miano  Eric G Wolfe  Steven R Alberts  Joleen M Hubbard  Harry H Yoon  Guido Francini
Institution:aDepartment of Experimental and Clinical Medicine, University of Florence, Florence 50134, Italy;bMayo Clinic, Rochester, MN, USA;cDepartment of Human Pathology and Oncology, University of Siena, Siena, Italy;dSanta Maria Alle Scotte Hospital, Siena, Italy;eDepartment of Medical and Surgical Sciences and Neuroscience, University of Siena, Siena, Italy
Abstract:BackgroundHigh tumor infiltrating lymphocytes (TILs) density was previously shown to be associated with favorable prognosis for patients with colon cancer (CC). However, the impact of TILs on overall survival (OS) of stage II CC patients who received adjuvant chemotherapy (ADJ) or not (no-ADJ) is unknown. We assessed the prognostic value of CD3+ TILs in stage II CC patients according to whether they had ADJ or not.MethodsPatients treated with curative surgery for stage II CC (2002–2013) were selected from the Santa Maria alle Scotte Hospital registry. TILs at the invasive front, center of tumor, and stroma were determined by immunohistochemistry and manually quantified as the rate of TILs/total tissue areas. High TILs (H-TILs) was defined as >20%. Patients were categorized as high or low TILs (L-TILs) and ADJ or no-ADJ.ResultsOf the 678 patients included, 137 (20%) received ADJ and 541 (80%) did not. The distribution of the 4 groups were: 16% (L-TIL/ADJ), 64% (L-TIL/no-ADJ), 5% (H-TIL/ADJ), 15% (H-TIL/no-ADJ). Compared to H-TILs/no-ADJ, ADJ patients showed a significantly increased OS (P<.01) regardless of the TILs rate whereas L-TILs/no-ADJ had significantly decreased OS and higher risk of death (HR=1.41; 95% CI, 1.06–1.88; P<.0001). On multivariable analysis, the unfavorable prognostic value of L-TILs (vs. H-TILs) for no-ADJ patients was confirmed (HR=1.36; 95% CI 1.02, 1.82; P=.0373).ConclusionLow CD3+ TILs rate was associated with shorter OS in those with stage II colon cancer who did not receive adjuvant therapy. Low CD3+ TILs could be considered an additional risk factor for still ADJ-untreated stage II CC patients, which could facilitate clinical decision making.
Keywords:Colorectal cancer  Post-surgery treatment  Fluoropyrimidines  Prognostic marker  T-cells
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