# Key immune cells in the tumor immune microenvironment of colorectal cancer: Roles and research advances (Review)

**Authors:** Ming Qiu, Chongyuan Lan, Minglin Lin, Hui Ma

PMC · DOI: 10.3892/or.2026.9057 · 2026-01-21

## TL;DR

This review explores how immune cells in the tumor environment affect colorectal cancer and highlights new immunotherapy approaches.

## Contribution

The paper provides a comprehensive overview of immune cell roles in CRC and emerging cell-based therapies.

## Key findings

- Immune cells in the tumor microenvironment can either suppress or promote colorectal cancer growth.
- Immune-checkpoint blockade shows promise, particularly in microsatellite instability-high tumors.
- Emerging cell-based immunotherapies may improve precision treatment for colorectal cancer.

## Abstract

Colorectal cancer (CRC) is the third most common cancer globally and the second leading cause of cancer-related mortalities. Surgery-centered multimodal therapy remains the cornerstone of care, yet outcomes are poor in advanced or drug-resistant disease. The tumor immune microenvironment (TIME), a network of immune cells, cytokines and stromal elements, shapes antitumor immunity and can either restrain or encourage tumor growth. Specific immune cells within the TIME influence CRC biology, while immune-checkpoint blockade has delivered notable benefits, especially in microsatellite instability-high tumors. The present review discusses the principal immune cell populations in the CRC TIME, outlines their mechanisms of action and discusses emerging cell-based immunotherapies that may guide future precision treatment.

## Linked entities

- **Diseases:** colorectal cancer (MONDO:0005575)

## Full-text entities

- **Genes:** GZMB (granzyme B) [NCBI Gene 3002] {aka C11, CCPI, CGL-1, CGL1, CSP-B, CSPB}, CTLA4 (cytotoxic T-lymphocyte associated protein 4) [NCBI Gene 1493] {aka ALPS5, CD, CD152, CELIAC3, CTLA-4, GRD4}, CTNNB1 (catenin beta 1) [NCBI Gene 1499] {aka CTNNB, EVR7, MRD19, NEDSDV, armadillo}, CCL4 (C-C motif chemokine ligand 4) [NCBI Gene 6351] {aka ACT2, AT744.1, G-26, HC21, LAG-1, LAG1}, CD163 (CD163 molecule) [NCBI Gene 9332] {aka M130, MM130, SCARI1}, FASLG (Fas ligand) [NCBI Gene 356] {aka ALPS1B, APT1LG1, APTL, CD178, CD95-L, CD95L}, NCAM1 (neural cell adhesion molecule 1) [NCBI Gene 4684] {aka CD56, MSK39, NCAM}, CCL18 (C-C motif chemokine ligand 18) [NCBI Gene 6362] {aka AMAC-1, AMAC1, CKb7, DC-CK1, DCCK1, MIP-4}, IL15 (interleukin 15) [NCBI Gene 3600] {aka IL-15}, CD274 (CD274 molecule) [NCBI Gene 29126] {aka ADMIO5, B7-H, B7H1, PD-L1, PDCD1L1, PDCD1LG1}, ERBB2 (erb-b2 receptor tyrosine kinase 2) [NCBI Gene 2064] {aka CD340, HER-2, HER-2/neu, HER2, MLN 19, MLN-19}, SPP1 (secreted phosphoprotein 1) [NCBI Gene 6696] {aka BNSP, BSPI, ETA-1, OPN}, IL17A (interleukin 17A) [NCBI Gene 3605] {aka CTLA-8, CTLA8, IL-17, IL-17A, IL17, ILA17}, FAS (Fas cell surface death receptor) [NCBI Gene 355] {aka ALPS1A, APO-1, APT1, CD95, FAS1, FASTM}, CD276 (CD276 molecule) [NCBI Gene 80381] {aka 4Ig-B7-H3, B7-H3, B7H3, B7RP-2}, LAMP3 (lysosome associated membrane protein 3) [NCBI Gene 27074] {aka CD208, DC LAMP, DC-LAMP, DCLAMP, LAMP, LAMP-3}, TGFB1 (transforming growth factor beta 1) [NCBI Gene 7040] {aka CAEND1, CED, DPD1, IBDIMDE, LAP, TGF-beta1}, IL2 (interleukin 2) [NCBI Gene 3558] {aka IL-2, TCGF, lymphokine}, IL10 (Interleukin 10 level) [NCBI Gene 103158318], KLRK1 (killer cell lectin like receptor K1) [NCBI Gene 396737] {aka NKG2D}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, IL5 (interleukin 5) [NCBI Gene 3567] {aka EDF, IL-5, TRF}, IL10 (interleukin 10) [NCBI Gene 3586] {aka CSIF, GVHDS, IL-10, IL10A, TGIF}, CD19 (CD19 molecule) [NCBI Gene 930] {aka B4, CVID3}, TRBV20OR9-2 (T cell receptor beta variable 20/OR9-2 (non-functional)) [NCBI Gene 6962] {aka CDR3, TCRBV20S2, TCRBV2O, TCRBV2S2O}, CD44 (CD44 molecule (IN blood group)) [NCBI Gene 960] {aka CDW44, CSPG8, ECM-III, ECMR-III, H-CAM, HCELL}, IFNG (interferon gamma) [NCBI Gene 3458] {aka IFG, IFI, IMD69}, IL4 (interleukin 4) [NCBI Gene 3565] {aka BCGF-1, BCGF1, BSF-1, BSF1, IL-4}, CSF1R (colony stimulating factor 1 receptor) [NCBI Gene 1436] {aka BANDDOS, C-FMS, CD115, CSF-1R, CSFR, FIM2}, BATF3 (basic leucine zipper ATF-like transcription factor 3) [NCBI Gene 55509] {aka JDP1, JUNDM1, SNFT}, CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}, MRC1 (mannose receptor C-type 1) [NCBI Gene 4360] {aka CD206, CLEC13D, CLEC13DL, MMR, MRC1L1, bA541I19.1}, CXCL13 (C-X-C motif chemokine ligand 13) [NCBI Gene 10563] {aka ANGIE, ANGIE2, BCA-1, BCA1, BLC, BLR1L}, CCL5 (C-C motif chemokine ligand 5) [NCBI Gene 6352] {aka D17S136E, RANTES, SCYA5, SIS-delta, SISd, TCP228}, IL13 (interleukin 13) [NCBI Gene 3596] {aka IL-13, P600}, CXCR2 (C-X-C motif chemokine receptor 2) [NCBI Gene 3579] {aka CD182, CDw128b, CMKAR2, IL8R2, IL8RA, IL8RB}, TIGIT (T cell immunoreceptor with Ig and ITIM domains) [NCBI Gene 100624099], CD4 (CD4 molecule) [NCBI Gene 920] {aka CD4mut, IMD79, Leu-3, OKT4D, T4}, HLA-C (major histocompatibility complex, class I, C) [NCBI Gene 3107] {aka D6S204, HLA-JY3, HLAC, HLC-C, MHC, PSORS1}, CD80 (CD80 molecule) [NCBI Gene 941] {aka B7, B7-1, B7.1, BB1, CD28LG, CD28LG1}, CD47 (CD47 molecule) [NCBI Gene 961] {aka IAP, MER6, OA3}, PDCD1 (programmed cell death 1) [NCBI Gene 5133] {aka ADMIO4, AIMTBS, CD279, PD-1, PD1, SLEB2}, IL12B (interleukin 12B) [NCBI Gene 3593] {aka CLMF, CLMF2, IL-12B, IMD28, IMD29, NKSF}, CD86 (CD86 molecule) [NCBI Gene 942] {aka B7-2, B7.2, B70, BU63, CD28LG2, CD86 v6}, CCL2 (C-C motif chemokine ligand 2) [NCBI Gene 6347] {aka GDCF-2, HC11, HSMCR30, MCAF, MCP-1, MCP1}, ANKRD22 (ankyrin repeat domain 22) [NCBI Gene 118932], CCR2 (C-C motif chemokine receptor 2) [NCBI Gene 729230] {aka CC-CKR-2, CCR-2, CCR2A, CCR2B, CD192, CKR2}, VEGFA (vascular endothelial growth factor A) [NCBI Gene 7422] {aka L-VEGF, MVCD1, VEGF, VPF}, ARG1 (arginase 1) [NCBI Gene 383], CD38 (CD38 molecule) [NCBI Gene 952] {aka ADPRC 1, ADPRC1, cADPR1}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, IL22 (interleukin 22) [NCBI Gene 50616] {aka IL-21, IL-22, IL-D110, IL-TIF, ILTIF, TIFIL-23}, EGFR (epidermal growth factor receptor) [NCBI Gene 1956] {aka ERBB, ERBB1, ERRP, HER1, NISBD2, NNCIS}, CD68 (CD68 molecule) [NCBI Gene 968] {aka GP110, LAMP4, SCARD1}, SIRPA (signal regulatory protein alpha) [NCBI Gene 140885] {aka BIT, CD172A, MFR, MYD-1, MYD1, P84}, FOXP3 (forkhead box P3) [NCBI Gene 50943] {aka AIID, DIETER, IPEX, JM2, PIDX, XPID}
- **Diseases:** MSI-H (MESH:D053842), solid (MESH:D018250), cytotoxic (MESH:D064420), mcdonough sarcoma (MESH:C538158), Tumor (MESH:D009369), tumorigenic (MESH:D002471), NET (MESH:C536657), lymph node (MESH:D000072717), metastases (MESH:D009362), inflammation (MESH:D007249), TAM (MESH:D020914), CRC (MESH:D015179)
- **Chemicals:** folinic acid (MESH:D002955), adenosine (MESH:D000241), prostaglandin E2 (MESH:D015232), oxaliplatin (MESH:D000077150), lactate (MESH:D019344), NO (MESH:D009569), xeloda and oxaliplatin (-), selicrelumab (MESH:C518149), ATP (MESH:D000255), ROS (MESH:D017382), emactuzumab (MESH:C000602304), LPS (MESH:D008070), fluorouracil (MESH:D005472), atezolizumab (MESH:C000594389)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606]
- **Cell lines:** N2 — Mus musculus (Mouse), Mouse neuroblastoma, Cancer cell line (CVCL_0470)

## Figures

2 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12854104/full.md

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Source: https://tomesphere.com/paper/PMC12854104