Abstract

Cancer associated fibroblasts (CAFs) and tumor associated macrophages (TAMs) are among the most important and abundant players of the tumor microenvironment. CAFs as well as TAMs are known to play pivotal supportive roles in tumor growth and progression. The number of CAF or TAM cells is mostly correlated with poor prognosis. Both CAFs and TAMs are in a reciprocal communication with the tumor cells in the tumor milieu. In addition to such interactions, CAFs and TAMs are also involved in a dynamic and reciprocal interrelationship with each other. Both CAFs and TAMs are capable of altering each other’s functions. Here, the current understanding of the distinct mechanisms about the complex interplay between CAFs and TAMs are summarized. In addition, the consequences of such a mutual relationship especially for tumor progression and tumor immune evasion are highlighted, focusing on the synergistic pleiotropic effects. CAFs and TAMs are crucial components of the tumor microenvironment; thus, they may prove to be potential therapeutic targets. A better understanding of the tri-directional interactions of CAFs, TAMs and cancer cells in terms of tumor progression will pave the way for the identification of novel theranostic cues in order to better target the crucial mechanisms of carcinogenesis.

Highlights

  • It is known that the tumor microenvironment consists of several different types of cells in addition to cancer cells such as immune cells, fibroblasts as well as capillaries, basement membrane and extracellular matrix (ECM) [1,2,3,4]

  • It was reported that the number of tumor associated macrophages (TAMs) in breast carcinoma is significantly correlated with the presence of Cancer associated fibroblasts (CAFs) [15]

  • Several issues still persist in terms of the effects of CAFs on tumor progression

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Summary

Gurcan Gunaydin*

The number of CAF or TAM cells is mostly correlated with poor prognosis Both CAFs and TAMs are in a reciprocal communication with the tumor cells in the tumor milieu. In addition to such interactions, CAFs and TAMs are involved in a dynamic and reciprocal interrelationship with each other. Both CAFs and TAMs are capable of altering each other’s functions. A better understanding of the tri-directional interactions of CAFs, TAMs and cancer cells in terms of tumor progression will pave the way for the identification of novel theranostic cues in order to better target the crucial mechanisms of carcinogenesis

INTRODUCTION
CANCER ASSOCIATED FIBROBLASTS
Origin of CAFs
Heterogeneity of CAFs
Activation of Fibroblasts
The Role of CAFs on Tumor Progression
TUMOR ASSOCIATED MACROPHAGES
Polarization of Macrophages
The Role of TAMs on Tumor Progression
THE INTERPLAY BETWEEN CAFs AND TAMs
Reciprocal Interactions
Recruitment and Polarization of TAMs by CAFs
The Effects on Tumor Progression
The Effects on Immune Evasion
Findings
DISCUSSION AND CONCLUDING

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