Prognostic significance of interleukin-17A-producing colorectal tumour antigen-specific T cells

Abstract

Background The T cell cytokine profile is a key prognostic indicator of post-surgical outcome for colorectal cancer (CRC). Whilst TH1 (IFN-γ+) cell-mediated responses generated in CRC are well documented and are associated with improved survival, antigen-specific TH17 (IL-17A+) responses have not been similarly measured. Methods We sought to determine the cytokine profile of circulating tumour antigen-(5T4/CEA) specific T cells of 34 CRC patients to address whether antigen-specific IL-17A responses were detectable and whether these were distinct to IFN-γ responses. Results As with IFN-γ-producing T cells, anti-5T4/CEA TH17 responses were detectable predominantly in early stage (TNM I/II) CRC patients. Moreover, whilst IL-17A was always produced in association with IFN-γ, this release was mainly from two distinct T cell populations rather than by ‘dual producing’ T cells. Patients mounting both tumour-specific TH1+/TH17+ responses exhibited prolonged relapse-free survival. Conclusions Tumour antigen-specific TH17 responses play a beneficial role in preventing post-operative colorectal tumour recurrence.

The Role of Inflammatory Cytokines in the Pathogenesis of Colorectal Carcinoma—Recent Findings and Review

“…In CRCs TME, IL-17 restricts immune surveillance, inhibits the infiltration of CD8+ T cells, recruits MDSCs by inducing G-CSF production, and promotes cancer-elicit inflammation, favoring the formation of cancer-supportive niches [ 143 , 144 , 145 ]. Nevertheless, the release of IL-17A by CEA-specific T cells after CRC surgery does not seem responsible for the poorer survival of those patients [ 146 ]. On the contrary, IL-17F expression seems to be usually downregulated in CRC cells [ 147 , 148 ].…”

“…Furthermore, overexpression of certain cytokines may influence the specific type of treatment. Increased serum levels of IL-6, IL-10, and IL-17A correlate with adverse prognosis in CRC patients undergoing adjuvant chemotherapy and may be useful in monitoring the efficacy of therapy [ 146 , 243 , 245 ]. The downregulation of other cytokines, such as IL-7, also correlated with a worse prognosis [ 49 ].…”