The Dark Knight: Functional Reprogramming of Neutrophils in the Pathogenesis of Colitis-Associated Cancer

Area of Science:

• Immunology
• Oncology
• Gastroenterology

Background:

• Neutrophils are key myeloid cells recruited to inflamed tissues, playing critical roles in colitis and the tumor microenvironment during colon cancer development.
• While essential for host defense against pathogens, neutrophils can adopt protumoral functions, contributing to tumor initiation, growth, and metastasis.
• The specific characteristics and functions of protumoral neutrophils in cancer patients remain incompletely defined.

Purpose of the Study:

• To review current knowledge on the fluctuating roles of neutrophils in the gut, specifically their transition between inflammatory and immunosuppressive states.
• To explore how neutrophils contribute to tumor development, particularly in the context of inflammation-driven colorectal cancer.
• To highlight the functional ambivalence of neutrophils within the colon tumor microenvironment for potential therapeutic exploitation.

Main Methods:

• Literature review of existing research on neutrophil function in inflammatory bowel diseases and colorectal cancer.
• Analysis of the dichotomous roles of neutrophils, encompassing both antitumoral and protumoral effects.
• Examination of the colon tumor microenvironment and the impact of neutrophil populations.

Main Results:

• Neutrophils exhibit a functional ambivalence, capable of both protecting the host and promoting tumor progression.
• In inflammatory conditions like colitis, neutrophils can contribute to inflammation-driven colorectal cancer.
• Protumoral neutrophils in cancer patients can be immunosuppressive and serve as markers for disease progression.

Conclusions:

• Neutrophil behavior in the gut is dynamic, shifting between inflammatory and immunosuppressive states that influence colon cancer development.
• The protumoral capacity of neutrophils presents a significant challenge in cancer progression and metastasis.
• Targeting the functional ambivalence of neutrophils offers potential therapeutic strategies to prevent or reverse inflammation-dependent colon cancer.