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Latest Advances in Targeting the Tumor Microenvironment for Tumor Suppression
Chloé Laplagne1,2,3, Marcin Domagala4,5,6, Augustin Le Naour7,8,9
1Centre de Recherches en Cancérologie de Toulouse, Inserm UMR1037, 31037 Toulouse, France. chloe.laplagne@inserm.fr.
Abstract:
The tumor bulk is composed of a highly heterogeneous population of cancer cells, as well as a large variety of resident and infiltrating host cells, extracellular matrix proteins, and secreted proteins, collectively known as the tumor microenvironment (TME). The TME is essential for driving tumor development by promoting cancer cell survival, migration, metastasis, chemoresistance, and the ability to evade the immune system responses. Therapeutically targeting tumor-associated macrophages (TAMs), cancer-associated fibroblasts (CAFs), regulatory T-cells (T-regs), and mesenchymal stromal/stem cells (MSCs) is likely to have an impact in cancer treatment. In this review, we focus on describing the normal physiological functions of each of these cell types and their behavior in the cancer setting. Relying on the specific surface markers and secreted molecules in this context, we review the potential targeting of these cells inducing their depletion, reprogramming, or differentiation, or inhibiting their pro-tumor functions or recruitment. Different approaches were developed for this targeting, namely, immunotherapies, vaccines, small interfering RNA, or small molecules.
Insights
The tumor microenvironment (TME) supports cancer growth and immune evasion. Targeting key TME cells like tumor-associated macrophages (TAMs) and cancer-associated fibroblasts (CAFs) offers promising new cancer treatment strategies.
Area of Science:
- Oncology
- Immunology
- Cell Biology
Background:
- The tumor microenvironment (TME) is a complex ecosystem crucial for tumor progression.
- It comprises cancer cells, host cells, extracellular matrix, and secreted factors.
- The TME influences cancer cell survival, metastasis, and therapeutic resistance.
Purpose of the Study:
- To review the normal functions and cancer-associated behaviors of key TME cell types.
- To explore therapeutic strategies targeting these cells for cancer treatment.
- To discuss methods for depleting, reprogramming, or inhibiting pro-tumor functions of TME cells.
Main Methods:
- Literature review focusing on the TME and its cellular components.
- Analysis of cell surface markers and secreted molecules for targeting.
- Examination of various therapeutic approaches including immunotherapies and small molecules.
Main Results:
- Identified tumor-associated macrophages (TAMs), cancer-associated fibroblasts (CAFs), regulatory T-cells (T-regs), and mesenchymal stromal/stem cells (MSCs) as critical TME components.
- Detailed their roles in promoting tumor development and immune evasion.
- Highlighted diverse strategies for targeting these cells.
Conclusions:
- Targeting specific TME cells holds significant potential for improving cancer therapy.
- Modulating TAMs, CAFs, T-regs, and MSCs can disrupt tumor growth and metastasis.
- Further research into novel targeting approaches is warranted.
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