Role of Cytokines and Chemokines in NSCLC Immune Navigation and Proliferation.

Sowmya Ramachandran,Faris Alrumaihi,Kapil Dev,Arshad Husain Rahmani,Deepti Bhatt,Yamini Goyal,Saleh A Almatroodi,Ahmad Almatroudi,Mohammed A Alsahli,Naushad Ahmad Khan,Amit K Verma,Jayeeta Ghose

doi:10.1155/2021/5563746

Abstract

With over a million deaths every year around the world, lung cancer is found to be the most recurrent cancer among all types. Nonsmall cell lung carcinoma (NSCLC) amounts to about 85% of the entire cases. The other 15% owes it to small cell lung carcinoma (SCLC). Despite decades of research, the prognosis for NSCLC patients is poorly understood with treatment options limited. First, this article emphasises on the part that tumour microenvironment (TME) and its constituents play in lung cancer progression. This review also highlights the inflammatory (pro- or anti-) roles of different cytokines (ILs, TGF-β, and TNF-α) and chemokine (CC, CXC, C, and CX3C) families in the lung TME, provoking tumour growth and subsequent metastasis. The write-up also pinpoints recent developments in the field of chemokine biology. Additionally, it covers the role of extracellular vesicles (EVs), as alternate carriers of cytokines and chemokines. This allows the cytokines/chemokines to modulate the EVs for their secretion, trafficking, and aid in cancer proliferation. In the end, this review also stresses on the role of these factors as prognostic biomarkers for lung immunotherapy, apart from focusing on inflammatory actions of these chemoattractants.

Highlights

Cancer, largely a result of random mutations, goes through a multistep process of carcinogenesis
The data in this study suggested that by targeting IL-27 in Nonsmall cell lung carcinoma (NSCLC), mi-RNA-935 acted as an oncomiRNA
This study identified the alteration of tumour microenvironment (TME) by IL-17B signalling and subsequent tumour growth induction

Summary

Introduction

Largely a result of random mutations, goes through a multistep process of carcinogenesis. In the TME, the most abundant immune system linked stromal cell type is TAMs [5] Since they are activated off and on, they lead to cancer progression, epithelial to mesenchymal transition (EMT), intrusion, and metastasis, resulting in shoddy prognosis. Inflammation supplies the tumour ME with bioactive molecules, stimulating chemokines, EMT, and growth factors [44] They prevent cell death leading to cell proliferation and enzymes that modify ECM, angiogenic promoting factors that enable tumour angiogenesis, invasion, and metastasis, aggravating progression of cancer [16, 41]. In the TME, these factors matter a lot in tumour progression and spread, besides therapy resistance Both cytokines (IL-6, 10, 17, 27, 35; TNF-α; IFN-γ; TGF-β) and chemokines (CCL-2, 5, 18; CCR-4; CXCR-4; CX3CL-1; CXCL-1, 5, 8, 13) are very commonly targeted for lung cancer treatment, considering their biomarker roles [5].

Role of Chemokines in Lung Cancer Therapy

Concluding Remarks

Findings

Future Directions