Regulatory (FoxP3+) T-cell Tumor Infiltration Is a Favorable Prognostic Factor in Advanced Colon Cancer Patients Undergoing Chemo or Chemoimmunotherapy

Antitumor immune response and chemotherapy-induced immunomodulation in colon cancer patients represented the rationale to design new strategies, like GOLFIG chemoimmunotherapy (gemcitabine, oxaliplatin, 5-fluorouracil/folinic acid, granulocyte macrophage colony-stimulating factor, and aldesleukine), that resulted a safe and very active regimen. Antitumor activity and immunity feedback to GOLFIG were strictly correlated with the best outcome observed in patients with autoimmunity signs, increase of central memory T cells, and decrease of regulatory T cells (T-reg) in the peripheral blood. We thus investigated a potential correlation between the T-reg tumor infiltration at diagnosis and the clinical outcome in a current randomized phase 3 trial aimed to compare the GOLFIG regimen with the standard FOLFOX chemotherapy (GOLFIG-2). An immunohistochemistry study was carried out to quantify the infiltration of T-reg/FoxP3(+) T lymphocytes in tumor samples of 57 patients enrolled in the GOLFIG-2 trial. T-reg tumor infiltration scores were correlated with overall survival, treatment-relative survival, and progression-free survival (PFS). Higher T-reg tumor infiltration scores were associated with a better prognosis in the whole series (T-reg high score vs. low score: overall survival = mean 43.2 mo vs. 28.6 mo, P = 0.0005) and a better outcome after treatment (T-reg high score vs. low score: PFS = mean 15.8 mo vs. 8.8 mo, P = 0.0009; treatment-relative survival = mean 23.1 mo vs. 18.2 mo, P = 0.004). PFS was significantly longer in GOLFIG high versus all other subgroups (mean 18.1 mo vs. 9.9 mo, P = 0.01). Our results suggest that a higher FoxP3(+) T-lymphocyte tumor infiltration score is a favorable prognostic factor in colon cancer patients undergoing chemo or chemoimmunotherapy.