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Tumour Microenvironment and Immune Evasion in EGFR Addicted NSCLC: Hurdles and Possibilities

Antonio Santaniello1, Fabiana Napolitano2, Alberto Servetto3

  • 1Department of Clinical Medicine and Surgery, University of Naples "Federico II", 80131 Naples, Italy. antonio.santaniello3@unina.it.

Cancers
|September 27, 2019
PubMed

Insights

Immune-checkpoint inhibitors improve survival in Non-Small Cell Lung Cancer (NSCLC). However, tumors with epidermal growth factor receptor (EGFR) mutations often resist this therapy, prompting research into underlying mechanisms.

Area of Science:

  • Oncology
  • Immunotherapy
  • Molecular Biology

Background:

  • Immune-checkpoint inhibitors, specifically anti-programmed cell death 1/programmed cell death ligand 1 (PD-1/PD-L1) therapy, have transformed Non-Small Cell Lung Cancer (NSCLC) treatment, enhancing progression-free and overall survival across various patient subgroups.
  • Despite broad efficacy, a subset of NSCLC patients does not respond to anti-PD-1/PD-L1 therapy. Tumors harboring epidermal growth factor receptor (EGFR) mutations represent a significant group of non-responders, and their inclusion in clinical trials and therapeutic evaluation is currently under investigation.

Purpose of the Study:

  • To elucidate the mechanisms of resistance to immune-checkpoint inhibitors in NSCLC, particularly in tumors with EGFR mutations.
  • To evaluate the role of the tumor microenvironment, including cellular components, cytokines, secreted factors, and angiogenesis, in mediating resistance to anti-PD-1/PD-L1 therapy.
  • To analyze the potential efficacy and application of immunotherapy in NSCLC patients with EGFR mutations.

Main Methods:

  • Comprehensive literature review focusing on preclinical and clinical studies.
  • Analysis of the tumor microenvironment's components and their interaction with tumor cells in the context of EGFR mutations.
  • Investigation of angiogenesis and immune cell infiltration patterns in EGFR-mutated NSCLC.

Main Results:

  • EGFR mutations are associated with resistance to anti-PD-1/PD-L1 therapy in NSCLC.
  • Specific characteristics of the tumor microenvironment, such as altered cytokine profiles and angiogenesis, contribute to immune evasion in EGFR-mutated tumors.
  • The interaction between tumor cells, the tumor microenvironment, and immune cells presents a complex landscape influencing immunotherapy response.

Conclusions:

  • Understanding the mechanisms of immunotherapy resistance in EGFR-mutated NSCLC is crucial for developing effective treatment strategies.
  • Targeting the tumor microenvironment and exploring novel immunotherapeutic approaches may overcome resistance in this patient population.
  • Further research and clinical trials are warranted to define the role of immunotherapy in EGFR-mutated NSCLC.
Keywords:
EGFR mutationICINSCLCTKITMBTMEangiogenesisimmune checkpoint inhibitorstumour microenvironmenttumour mutational burden

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