Emerging role of chemokines in small cell lung cancer: Road signs for metastasis, heterogeneity, and immune response

Parvez Khan, Mahek Fatima, Md Arafat Khan, Surinder Kumar Batra, Mohd Wasim Nasser

Research output: Contribution to journalReview articlepeer-review

13 Scopus citations

Abstract

Small cell lung cancer (SCLC) is a recalcitrant, relatively immune-cold, and deadly subtype of lung cancer. SCLC has been viewed as a single or homogenous disease that includes deletion or inactivation of the two major tumor suppressor genes (TP53 and RB1) as a key hallmark. However, recent sightings suggest the complexity of SCLC tumors that comprises highly dynamic multiple subtypes contributing to high intratumor heterogeneity. Furthermore, the absence of targeted therapies, the understudied tumor immune microenvironment (TIME), and subtype plasticity are also responsible for therapy resistance. Secretory chemokines play a crucial role in immunomodulation by trafficking immune cells to the tumors. Chemokines and cytokines modulate the anti-tumor immune response and wield a pro-/anti-tumorigenic effect on SCLC cells after binding to cognate receptors. In this review, we summarize and highlight recent findings that establish the role of chemokines in SCLC growth and metastasis, and sophisticated intratumor heterogeneity. We also discuss the chemokine networks that are putative targets or modulators for augmenting the anti-tumor immune responses in targeted or chemo-/immuno-therapeutic strategies, and how these combinations may be utilized to conquer SCLC.

Original languageEnglish (US)
Pages (from-to)117-126
Number of pages10
JournalSeminars in Cancer Biology
Volume87
DOIs
StatePublished - Dec 2022

Keywords

  • CCL5, neuroendocrine tumors
  • CXCL10
  • CXCR4
  • Small cell lung cancer
  • Subtype switching

ASJC Scopus subject areas

  • Cancer Research

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