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.

Highlights

  • Worldwide, Lung cancer is responsible for the highest number of cancer-related death in men and women [1]

  • Cytokines and chemokines produced by tumor-infiltrating immune cells play a significant role in tumor development, progression, metastasis, and therapy resistance; they widely used as diagnostic and prognostic biomarkers in the treatment of cancer

  • In the in vivo metastasis lung tumor model and human lung cancer biopsies, infiltration of Tumor-associated macrophages (TAMs) was found to be increased by nuclear factor kappa B subunit 1 (NFKB1)-CCL2 signaling via an elevation in neddylation pathway [135]

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Summary

INTRODUCTION

Lung cancer is responsible for the highest number of cancer-related death in men and women [1]. Tumor cell-derived colony stimulating factor 1 (CSF1) promotes macrophage infiltration in the necrotic tumor area [32,33,34] These TAMs further support angiogenesis and invasion, and more interestingly, their highdensity associated with reduced relapse-free survival [35, 36]. Cytokines and chemokines produced by tumor-infiltrating immune cells play a significant role in tumor development, progression, metastasis, and therapy resistance; they widely used as diagnostic and prognostic biomarkers in the treatment of cancer. In this review, we summarized the published literature from the year 2000 to the year 2019, focusing on the role of IL6, TNFα, IL10, CCL2, CX3CL1, IL8 in the macrophages-tumor cells crosstalk; leading to lung cancer development and progression

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