CRISPR in Lung Cancer Immunology: Myeloid Reprogramming and Checkpoint Resistance Mechanisms

Lung cancer remains a leading cause of cancer-related mortality worldwide, with immune checkpoint inhibitors (ICIs) offering meaningful but still limited clinical benefit. A major challenge is both primary and acquired resistance to immunotherapy, much of which is driven by complex interactions within the tumor microenvironment. In particular, myeloid cell populations—including tumor-associated macrophages, myeloid-derived suppressor cells, and dendritic cells—play central roles in shaping immune suppression, limiting T cell activity, and promoting resistance to checkpoint blockade.CRISPR-based genome editing technologies have rapidly transformed our ability to interrogate and manipulate immune and tumor cell biology with high precision. In lung cancer, these tools are enabling systematic dissection of the genetic and epigenetic programs that govern myeloid cell function, immune evasion, and therapeutic resistance. From pooled CRISPR screens to in vivo editing models, researchers can now identify key regulators of antigen presentation, interferon signaling, cytokine networks, and checkpoint pathways that influence treatment response.This Research Topic aims to bring together innovative studies that leverage CRISPR and related genome editing approaches to advance our understanding of lung cancer immunology, with a particular focus on myeloid reprogramming and resistance to immunotherapy. We welcome original research, reviews, and perspectives that address topics including, but not limited to:1. CRISPR-based functional genomics to identify regulators of myeloid cell polarization and immunosuppressive activity2. Mechanisms of resistance to immune checkpoint blockade uncovered through genome-wide or targeted editing approaches3. Epigenetic and transcriptional reprogramming of myeloid cells using CRISPR tools (e.g., CRISPRi/a, base editing)4. Development of in vitro and in vivo CRISPR-engineered models to study tumor–immune interactions in lung cancer5. Targeting tumor-intrinsic pathways that modulate immune recognition and response6. Combinatorial strategies integrating genome editing with immunotherapy7. Advances in delivery systems for genome editing in immune cells within the tumor microenvironmentBy integrating genome editing technologies with immunology and translational oncology, this Topic seeks to uncover actionable mechanisms of immune resistance and identify new strategies to enhance the efficacy of immunotherapy in lung cancer. Topic editors: Pushpanathan Muthuirulan, Joyce Tse, Salauddin Al Azad Source: https://www.frontiersin.org/research-topics/79957/crispr-in-lung-cancer-immunology-myeloid-reprogramming-and-checkpoint-resistance-mechanisms