Breaking barriers in lung cancer immunotherapy: overcoming resistance through TME insights and personalized care for special populations

Lung cancer remains one of the leading causes of cancer-related mortality globally, and immunotherapy has significantly reshaped therapeutic possibilities. While immune checkpoint inhibitors have transformed outcomes for subsets of patients, a substantial proportion still experience primary or acquired resistance. Increasing evidence suggests that the tumor microenvironment (TME)—comprising immune infiltrates, stromal components, vasculature, and metabolic cues—plays a central role in shaping therapeutic response. At the same time, real-world patient populations are diverse. Individuals with autoimmune disease, chronic viral infections, organ dysfunction, advanced age, or prior transplants remain understudied and underrepresented in clinical trials. Their unique biology and clinical considerations present an urgent need for tailored strategies. Understanding how TME biology intersects with the complexities of special populations offers a novel path toward more inclusive, precise, and effective immunotherapy.The goal of this collection is to showcase research that addresses unmet needs in the use of immunotherapy as a therapeutic strategy for lung cancer. Specifically, this collection aims to:1. Advance understanding of immunotherapy resistance, highlighting studies that unravel mechanisms driving primary and secondary resistance, particularly those rooted in the tumor microenvironment.2. Promote research focused on access, equity, and under‑represented populations, including studies addressing disparities in clinical trial representation.3. Integrate insights from TME biology, emerging biomarkers, and innovative therapeutic combinations to identify strategies that enhance immunotherapy responsiveness.4. Encourage contributions that consider real‑world complexities—especially in special populations such as individuals with autoimmune disease, organ dysfunction, chronic infections, or advanced age. This Research Topic invites submissions that explore the evolving role of immunotherapy in lung cancer, with an emphasis on understanding resistance mechanisms and improving care for under‑represented patient groups. We welcome contributions that examine:• Primary and acquired immune resistance pathways• Novel biomarkers and predictive tools for treatment selection• Innovative immunotherapy combinations to overcome resistance or toxicity• Access, disparities, and representation of special populations in clinical trials• Real‑world evidence and management considerations for patients with autoimmune disease, organ dysfunction, chronic infections, or advanced age• Clinical trials that focus on special populations (for those who are typically excluded from clinical trials), rare disease types• Commentaries, review articles, and case series pertaining to any of the above topics will be considered on a case-by-case basisPlease note that manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by robust and relevant validation (clinical cohort or biological validation in vitro or in vivo) are out of scope for this Research Topic.Nagashree Seetharamu COI: I have been in advisory/consultation engagements with the following: EMD Serono, AstraZeneca, Jazz, Regeneron, Genentech, Boehringer Ingelheim, Johnson and Johnson, Amgen, Nuvalent, Merck, Coherus. I have received research funding from: Lilly, Astra Zeneca, BMSDr Laura Mezquita COI: Lectures and educational activities: Bristol-Myers Squibb, AstraZeneca, Roche, Takeda, Radonova, Janssen, MSD, BeOne, BeOne. Consulting, advisory role: Roche, Takeda, AstraZeneca, Janssen, MSD, Pfizer. Research Grants: Inivata, Gilead, AstraZeneca, Tempus. Travel, Accommodations, Expenses: Roche, Takeda, AstraZeneca, Janssen, Regeneron. Topic editors: Nagashree Seetharamu, Laura Mezquita Source: https://www.frontiersin.org/research-topics/78377/breaking-barriers-in-lung-cancer-immunotherapy-overcoming-resistance-through-tme-insights-and-personalized-care-for-special-populations