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Review
. 2020 Mar 11:10:324.
doi: 10.3389/fonc.2020.00324. eCollection 2020.

Macrophage and Tumor Cell Cross-Talk Is Fundamental for Lung Tumor Progression: We Need to Talk

Poonam Sarode  1 , Martina Barbara Schaefer  2 , Friedrich Grimminger  2 , Werner Seeger  1   2 , Rajkumar Savai  1   2   3
Affiliations
Review

Macrophage and Tumor Cell Cross-Talk Is Fundamental for Lung Tumor Progression: We Need to Talk

Poonam Sarode et al. Front Oncol. .

Abstract

Regardless of the promising results of certain immune checkpoint blockers, current immunotherapeutics have met a bottleneck concerning response rate, toxicity, and resistance in lung cancer patients. Accumulating evidence forecasts that the crosstalk between tumor and immune cells takes center stage in cancer development by modulating tumor malignancy, immune cell infiltration, and immune evasion in the tumor microenvironment (TME). Cytokines and chemokines secreted by this crosstalk play a major role in cancer development, progression, and therapeutic management. An increased infiltration of Tumor-associated macrophages (TAMs) was observed in most of the human cancers, including lung cancer. In this review, we emphasize the role of cytokines and chemokines in TAM-tumor cell crosstalk in the lung TME. Given the role of cytokines and chemokines in immunomodulation, we propose that TAM-derived cytokines and chemokines govern the cancer-promoting immune responses in the TME and offer a new immunotherapeutic option for lung cancer treatment.

Keywords: chemokines; cytokines; lung cancer; tumor microenvironment; tumor-associated macrophages.

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Figures

Figure 1
Figure 1
Macrophage-Tumor cells crosstalk via cytokines and chemokines through an autocrine and paracrine manner is important for lung cancer development. In the TME, cytokines, and chemokines secreted by macrophages (IL-6, -10, CCL-2, -3, -4, -5, -18, -20, CX3CL1, TGFβ, VEGF, TNFα, etc.) and tumor cells (IL-6, -8, -10, TNFα, CCL-2, -3, -4, -5, -18, -20, CX3CL1, MMPs, etc.) induce phenotypic and functional changes in both the cell types. Macrophage secretome influences tumor growth, angiogenesis, invasion, metastasis, and immune evasion by the tumor cell, while secretory factors from tumor cells regulate monocyte/macrophage infiltration, activation and polarization toward pro-tumor M2-like TAMs phenotype. Abbreviations: CCL, chemokine ligand; CXCL, chemokine (C-X-C motif) ligand; IL, interleukin; MMPs, matrix metalloproteinase; TGFβ, transforming growth factor β; TNFα, tumor necrosis factor α; VEGF, vascular endothelial growth factor.
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