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Peer-reviewedCC BY 4.0International Journal of Molecular Sciences

Tumor-Centric Immune Crosstalk in Colorectal and Gastric Cancer: Molecular Mechanisms Linking Tumor Cells to Macrophages and CD8+ T Lymphocytes

  • Andrei Pascu1,2
  • Victor Ianole1,3
  • Mihai Danciu1,2
  1. 1Department of Morpho-Functional Sciences I, “Grigore T. Popa” University of Medicine and Pharmacy Iași, 16 University Street, 700115 Iasi, Romania
  2. 2Pathology Department, “Sf. Spiridon” University Emergency County Hospital, 1 Independentei Avenue, 700111 Iasi, Romania
  3. 3Pathology Department, “Prof. Dr. Nicolae Oblu” Emergency Clinical Hospital, 2 Ateneului Street, 700309 Iasi, Romania
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Abstract

Digestive malignancies remain a major cause of cancer-related mortality, with tumor progression (TP) being strongly influenced by the complex interactions between tumor cells (TCs) and their microenvironment. This review summarizes recently described mechanisms of interactions between tumor cells, macrophages and CD8+ T lymphocytes in colorectal and gastric cancer. PubMed and Web of Science were searched for studies published between 2020 and 2026, with the final search being conducted on 8 July 2026. Experimental and clinical studies, together with relevant reviews, were considered to examine these interactions and their therapeutic implications. The evidence shows a bilateral crosstalk in which tumor cells influence immune cell phenotype and function, while immune cells can further support or restrict tumor progression. These interactions involve receptor-ligand systems and paracrine signaling, followed by changes in intracellular pathways regulating proliferation, invasion, macrophage polarization and CD8+ T-cell exhaustion. Considerable methodological heterogeneity among studies limits a direct comparison of the reported mechanisms. Several therapeutic approaches targeting these interactions are currently being investigated in early-phase clinical trials. However, many components of tumor–immune crosstalk and their connections remain incompletely understood. A further characterization of these mechanisms may help identify therapeutic strategies able to interfere with the immunosuppressive microenvironment of colorectal and gastric cancers.

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Cite

BibTeXRIS
BibTeX
@article{pascu2026tumorcentric,
  title = {{Tumor-Centric Immune Crosstalk in Colorectal and Gastric Cancer: Molecular Mechanisms Linking Tumor Cells to Macrophages and CD8+ T Lymphocytes}},
  author = {Andrei Pascu and Victor Ianole and Mihai Danciu},
  journal = {International Journal of Molecular Sciences},
  year = {2026},
  month = oct,
  doi = {10.3390/ijms27209346},
  url = {https://www.mdpi.com/1422-0067/27/20/9346},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Tumor-Centric Immune Crosstalk in Colorectal and Gastric Cancer: Molecular Mechanisms Linking Tumor Cells to Macrophages and CD8+ T Lymphocytes
AU  - Andrei Pascu
AU  - Victor Ianole
AU  - Mihai Danciu
PY  - 2026
DA  - 2026/10/21
JO  - International Journal of Molecular Sciences
DO  - 10.3390/ijms27209346
UR  - https://www.mdpi.com/1422-0067/27/20/9346
AB  - Digestive malignancies remain a major cause of cancer-related mortality, with tumor progression (TP) being strongly influenced by the complex interactions between tumor cells (TCs) and their microenvironment. This review summarizes recently described mechanisms of interactions between tumor cells, macrophages and CD8+ T lymphocytes in colorectal and gastric cancer. PubMed and Web of Science were searched for studies published between 2020 and 2026, with the final search being conducted on 8 July 2026. Experimental and clinical studies, together with relevant reviews, were considered to examine these interactions and their therapeutic implications. The evidence shows a bilateral crosstalk in which tumor cells influence immune cell phenotype and function, while immune cells can further support or restrict tumor progression. These interactions involve receptor-ligand systems and paracrine signaling, followed by changes in intracellular pathways regulating proliferation, invasion, macrophage polarization and CD8+ T-cell exhaustion. Considerable methodological heterogeneity among studies limits a direct comparison of the reported mechanisms. Several therapeutic approaches targeting these interactions are currently being investigated in early-phase clinical trials. However, many components of tumor–immune crosstalk and their connections remain incompletely understood. A further characterization of these mechanisms may help identify therapeutic strategies able to interfere with the immunosuppressive microenvironment of colorectal and gastric cancers.
SN  - 1422-0067
ER  -