Both CD8+ and CD4+ T regulatory cells are associated with poor survival in colorectal cancer

Abstract Previous studies in colorectal cancer have linked high levels of FoxP3+ regulatory T-cells (Treg) (CRC) to a favourable prognosis. However, this contradicts the well-established immunosuppressive function of Treg. We resolved this conundrum using multiplex immunohistochemistry to characterise Foxp3 + and IL-10 + Treg in 1000 consecutively recruited patients’ tumours. Although Foxp3 + cells were associated with improved outcomes, this effect was confounded by high numbers of CD8+ effector T-cells (Teff). In contrast, a high percentage of CD8 + Treg to CD8 + Teff cells correlated with poor survival. Although the total CD4 + T-cell count was not prognostic, CD4+Teff were linked to improved outcomes, suggesting that the Treg fraction within the population may mask beneficial immune responses. Spatial proximity (