Work

Reprogramming Antitumor Immunity: NK Cell Strategies to Navigate the Immunosuppressive Tumor Microenvironment

Year: 2026

Type: article

Abstract: Tumor immune escape is a major barrier to durable cancer immunotherapy, as advanced malignancies create a tumor microenvironment (TME) that preferentially exhausts and disables T cell responses. While most approved cell therapies are T cell-based, this limitation motivates the exploration of an alternative effector cell platform. Natural killer (NK) cells, innate cytotoxic lymphocytes capable of antigen-independent recognition and killing, offer a compelling foundation for next-generation therapies with an improved safety profile. In this review, we first outline the cellular, molecular, and metabolic features of the immunosuppressive TME that restrict cytotoxic lymphocyte function, emphasizing mechanisms that limit immune cell-mediated responses. We then summarize key aspects of NK cell biology that can circumvent these barriers and critically evaluate current NK-based strategies, including engineered chimeric antigen receptor (CAR)-NK products and metabolic and trafficking interventions. Finally, we highlight emerging in vivo viral and mRNA/lipid nanoparticle platforms for CAR-NK generation and their potential to enhance scalability and therapeutic durability.

Source: Advanced Science

DOI: 10.1002/advs.75326

Authors: Tereza Kochs, Pranay Nath, Alice Chen, Rizwan Romee, Andreia Maia

Institutions: Harvard University, Dana-Farber Cancer Institute

Language: English

Topic: Immune Cell Function and Interaction

Subfield: Immunology

Field: Immunology and Microbiology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $6,730