Decoding the CAF-TAM axis: multi-omics dissection and therapeutic targeting of stromal-immune crosstalk in the tumor

Yage Fu1, Mei Li1, Shiwang Wu1

  • 1Department of Oral Pathology, School of Stomatology, Hainan Medical University, Haikou, 571199, P. R. China.

Cell Death & Disease
|April 18, 2026
PubMed

Insights

Cancer-associated fibroblasts (CAFs) and tumor-associated macrophages (TAMs) are key players in the tumor microenvironment, driving immune evasion and treatment resistance. Understanding their complex interactions is crucial for developing new cancer therapies.

Area of Science:

  • Oncology
  • Immunology
  • Cell Biology

Background:

  • Cancer-associated fibroblasts (CAFs) and tumor-associated macrophages (TAMs) are critical stromal and immune cells within the tumor microenvironment (TME).
  • These cells are known to promote immune evasion, metabolic reprogramming, and resistance to cancer therapies.
  • Their close structural and functional relationship is evident, with CAF-rich regions often showing significant TAM infiltration.

Purpose of the Study:

  • To review recent advances in understanding the heterogeneity, evolution, and signaling between CAFs and TAMs.
  • To summarize findings from transcriptomic, epigenomic, metabolomic, and spatial multi-omics studies.
  • To discuss therapeutic strategies targeting CAF-TAM interactions for enhanced antitumor efficacy.

Main Methods:

  • Review of single-cell, multi-omics, and spatial profiling technologies.
  • Analysis of transcriptomic, epigenomic, metabolomic, and spatial multi-omics data.
  • Synthesis of current knowledge on CAF and TAM subpopulations and their communication.

Main Results:

  • Identification of diverse CAF and TAM subpopulations and their complex intercellular communication networks.
  • Elucidation of their collective roles in extracellular matrix remodeling, immune suppression, metabolic adaptation, and angiogenesis.
  • Highlighting the spatiotemporal heterogeneity and lineage evolution of CAFs and TAMs.

Conclusions:

  • Targeting CAFs, TAMs, and their interactive pathways offers promising therapeutic strategies.
  • Reprogramming the immunosuppressive TME by modulating CAF-TAM interactions can enhance antitumor efficacy.
  • Emerging multi-omics technologies provide new conceptual and translational insights into cancer immunology and therapy.