Significant and Conflicting Correlation of IL-9 With and in Human Colorectal Cancer

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2021 Jan 25

PMID 33488574

Citations 35

Authors

Elena Niccolai

Edda Russo

Simone Baldi

Federica Ricci

Giulia Nannini

Matteo Pedone

Francesco Claudio Stingo

Antonio Taddei

Maria Novella Ringressi

Paolo Bechi

Alessio Mengoni

Renato Fani

Giovanni Bacci

Camilla Fagorzi

Carolina Chiellini

Domenico Prisco

Matteo Ramazzotti

Amedeo Amedei

Affiliations

Soon will be listed here.

Abstract

Background And Aim: Gut microbiota (GM) can support colorectal cancer (CRC) progression by modulating immune responses through the production of both immunostimulatory and/or immunosuppressive cytokines. The role of IL-9 is paradigmatic because it can either promote tumor progression in hematological malignancies or inhibit tumorigenesis in solid cancers. Therefore, we investigate the microbiota-immunity axis in healthy and tumor mucosa, focusing on the correlation between cytokine profile and GM signature.

Methods: In this observational study, we collected tumor (CRC) and healthy (CRC-S) mucosa samples from 45 CRC patients, who were undergoing surgery in 2018 at the Careggi University Hospital (Florence, Italy). First, we characterized the tissue infiltrating lymphocyte subset profile and the GM composition. Subsequently, we evaluated the CRC and CRC-S molecular inflammatory response and correlated this profile with GM composition, using Dirichlet multinomial regression.

Results: CRC samples displayed higher percentages of Th17, Th2, and Tregs. Moreover, CRC tissues showed significantly higher levels of MIP-1α, IL-1α, IL-1β, IL-2, IP-10, IL-6, IL-8, IL-17A, IFN-γ, TNF-α, MCP-1, P-selectin, and IL-9. Compared to CRC-S, CRC samples also showed significantly higher levels of the following genera: , , , , and . Finally, the abundance of spp. in CRC samples negatively correlated with IL-17A and positively with IL-9. On the contrary, spp. presence negatively correlated with IL-9.

Conclusions: Our data consolidate antitumor immunity impairment and the presence of a distinct microbiota profile in the tumor microenvironment compared with the healthy mucosa counterpart. Relating the CRC cytokine profile with GM composition, we confirm the presence of bidirectional crosstalk between the immune response and the host's commensal microorganisms. Indeed, we document, for the first time, that spp. and spp. are, respectively, positively and negatively correlated with IL-9, whose role in CRC development is still under debate.

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