Current and future immunotherapies for NSCLC

Area of Science:

• Oncology
• Immunology
• Genetics

Background:

• Non-small cell lung cancer (NSCLC) is a leading cause of cancer mortality globally.
• Immune checkpoint inhibitors (ICIs) targeting PD-1/PD-L1 and CTLA-4 have revolutionized NSCLC treatment.
• The expansion of immunotherapy into early-stage NSCLC represents a significant paradigm shift.

Purpose of the Study:

• To provide a comprehensive narrative review of the evolution of NSCLC immunotherapy.
• To examine current challenges in immunotherapy, including resistance mechanisms and biomarker development.
• To explore next-generation immunotherapeutic strategies for NSCLC.

Main Methods:

• Narrative review synthesizing current literature on NSCLC immunotherapy.
• Analysis of clinical challenges, genomic alterations (e.g., KRAS, STK11, KEAP1), and biomarker evolution.
• Exploration of emerging therapeutic modalities and future directions.

Main Results:

• Immunotherapy has evolved from advanced-stage treatments to neoadjuvant, adjuvant, and perioperative strategies in early-stage NSCLC.
• Key challenges include optimizing treatment duration, managing brain metastases, immune-related adverse events, and overcoming resistance.
• The biomarker landscape is expanding beyond PD-L1 to include ctDNA, microbiome, and TCR clonality.

Conclusions:

• Significant advancements in NSCLC immunotherapy have been achieved, particularly with the integration into early-stage disease.
• Refining biomarker-driven patient selection and optimizing combination therapies are crucial for improving long-term survival.
• Next-generation strategies hold promise for further enhancing treatment efficacy and overcoming resistance mechanisms in NSCLC.