# Cellular characteristics of the immune microenvironment of colorectal cancer and progress in immunotherapy research

## TL;DR

This review explores how the immune environment in colorectal cancer influences treatment and highlights new immunotherapy strategies to improve outcomes.

## Contribution

The paper provides a comprehensive synthesis of immune mechanisms and emerging immunotherapies, focusing on overcoming resistance in microsatellite-stable tumors.

## Key findings

- Immune evasion in CRC involves complex interactions among immune cells and non-cellular elements in the tumor microenvironment.
- Current immunotherapies show limited efficacy in microsatellite-stable tumors, necessitating novel combinatorial approaches.
- Targeting immune-metabolic interactions and spatial dynamics offers promising translational strategies for improved immunotherapy.

## Abstract

Colorectal cancer (CRC) continues to represent a major cause of cancer-related mortality worldwide, with its progression and therapeutic outcomes strongly shaped by the complexity and heterogeneity of the tumor immune microenvironment (TME). This review critically examines the cellular and molecular mechanisms driving immune evasion in CRC, emphasizing the dual roles of immune cell populations—including tumor-associated macrophages, neutrophils, dendritic cells, T cells, B cells, and natural killer cells—as well as non-cellular elements such as the extracellular matrix and extracellular vesicles.

A key objective is to evaluate recent developments in immunotherapeutic approaches, including immune checkpoint inhibitors, tumor vaccines, adoptive cell transfer, and novel combinatorial regimens, while addressing their therapeutic promise and inherent limitations, especially in microsatellite-stable (MSS) tumors that exhibit primary resistance to standard immunotherapies. Further analysis integrates perspectives on metabolic reprogramming within the TME, epigenetic alterations, and advances in engineered cellular therapies, thereby providing a comprehensive framework for overcoming immunosuppressive mechanisms.

Special consideration is directed toward the translational value of targeting immune-metabolic interactions and spatial dynamics within the TME. Ultimately, this work synthesizes current knowledge and outlines forward-looking strategies to advance personalized, multi-target immunotherapy, with the potential to reshape clinical paradigms in CRC management.