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Review
. 2022 Oct 17;29(1):83.
doi: 10.1186/s12929-022-00866-3.

Tumor microenvironment: barrier or opportunity towards effective cancer therapy

Aadhya Tiwari #  1 , Rakesh Trivedi #  2 , Shiaw-Yih Lin  3
Affiliations
Review

Tumor microenvironment: barrier or opportunity towards effective cancer therapy

Aadhya Tiwari et al. J Biomed Sci. .

Abstract

Tumor microenvironment (TME) is a specialized ecosystem of host components, designed by tumor cells for successful development and metastasis of tumor. With the advent of 3D culture and advanced bioinformatic methodologies, it is now possible to study TME's individual components and their interplay at higher resolution. Deeper understanding of the immune cell's diversity, stromal constituents, repertoire profiling, neoantigen prediction of TMEs has provided the opportunity to explore the spatial and temporal regulation of immune therapeutic interventions. The variation of TME composition among patients plays an important role in determining responders and non-responders towards cancer immunotherapy. Therefore, there could be a possibility of reprogramming of TME components to overcome the widely prevailing issue of immunotherapeutic resistance. The focus of the present review is to understand the complexity of TME and comprehending future perspective of its components as potential therapeutic targets. The later part of the review describes the sophisticated 3D models emerging as valuable means to study TME components and an extensive account of advanced bioinformatic tools to profile TME components and predict neoantigens. Overall, this review provides a comprehensive account of the current knowledge available to target TME.

Keywords: 3D models; CAR-T/NK therapy; Cancer immunotherapy; Checkpoint inhibitors; Specialized microenvironment; TME profiling; Tumor microenvironment.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Tumor microenvironment (TME): TME is a complex ecosystem of cellular. niche, acidic niche, inflammation etc. Extracellular matrix (ECM), the major non-cellular and acellular components, and several specialized microenvironments such as hypoxic component, provides architectural support, and act as a store house for factors such as chemokines, cytokines, growth factors etc., required for continuous tumor transformation process. Cellular components consist of non-immune and immune cell populations. Non- immune cell types include tumor cell, cancer associated fibroblast (CAF), neuron, and endothelial cell (blood vessel) that helps in tumor invasion, progression, and metastasis. Immune cells within TME comprise of tumor-associated macrophages (TAMs), tumor- associated neutrophils (TANs), dendritic cell (DCs), regulatory T cell (Treg), B cell, Natural killer (NK) cell, and cytotoxic T lymphocytes (CTLs). In immuno-competent conditions, CTL identifies and bring about tumor cell killing by releasing cytotoxic molecules such as granzyme-B, interferon-γ (IFN-γ), perforins etc. The figure is prepared by using BioRender software and publication license is obtained
Fig. 2
Fig. 2
Targeting different TME components for cancer therapy: Current strategies available for targeting major TME components for effective cancer therapy are shown. A Targeting inflammation, B targeting hypoxic TME, C targeting TME nerve supply, D targeting TME vascularization and cellular components like E targeting cancer associated fibroblasts (CAFs), targeting innate immune components by F Inducing M1Polarization, G Inhibiting M2 Polarization, H targeting Neutrophils, I targeting Natural Killer cells, J targeting Dendritic cells, and targeting adaptive immune components by K Activation of CTLs and L Targeting B cells are promising targets. Various drugs/inhibitors/antibodies targeting these components are in preclinical studies, under clinical trial or FDA approved for cancer treatment. The figure is prepared by using BioRender software and publication license is obtained
See this image and copyright information in PMC

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