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

Abstract

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 (Treg) in the peripheral blood. We thus investigated a potential correlation between the Treg 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 Treg/FoxP3+ T lymphocytes in tumor samples of 57 patients enrolled in the GOLFIG-2 trial. Treg tumor infiltration scores were correlated with overall survival, treatment-relative survival, and progression-free survival (PFS). Higher Treg tumor infiltration scores were associated with a better prognosis in the whole series (Treg high score vs. low score: overall survival=mean 43.2 mo vs. 28.6 mo, P=0.0005) and a better outcome after treatment (Treg 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.

Human tumor‐induced and naturally occurring Treg cells differentially affect NK cells activated by either IL‐2 or target cells

“…This situation reflects the steadystate or homeostatic conditions within a given tumor tissue or tumor microenvironment. The clinical correlates for our in vitro findings are those patients and clinical studies of solid as well as non-solid tumors in which investigators found tumor-infiltrating Treg cells to be a good prognostic factor [29][30][31][32]. Examples include lymphomas as Hodgkin lymphoma where investigators found a positive correlation between high Treg cell infiltration and higher rates of survival [32].…”

“…1 Treg cells in colorectal cancer [30,33]. Further, Badoual et al reported that Treg cells are positively correlated with locoregional control in patients with head and neck cancer.…”

Tumor-infiltrating CD39+γδTregs are novel immunosuppressive T cells in human colorectal cancer

“…10,11 However, the role of Tregs in human CRC patients is still controversial. [12][13][14][15][16] Given the inconsistent results concerning the prognostic value of Tregs in patients with CRC, it is not surprising that there is to date no clinical trial reporting effective immunotherapies targeting Tregs in CRC. Therefore, it is drastically needed to understand the exact role of those regulatory T cells in human CRC.…”

Target Therapy in Platinum-Refractory/Resistant Ovarian Cancer: From Preclinical Findings to Current Clinical Practice

“…Tumor infiltration by different inflammatory cells has been correlated with prognosis and tumor progression in different tumors including EOC [95][96][97][98]. Among these cells, tumor associated macrophages (TAMs) have recently demonstrated to exert a significant immune suppressive effect together with a pro-angiogenic activity (M2 polarization) [99].…”