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Updated: Jul 20, 2025
Advances in Human Induced Pluripotent Stem Cell-Derived Chimeric Antigen Receptor-Expressing Natural Killer Cells
Published on: February 14, 2025
Harnessing Natural Killer Cells for Lung Cancer Therapy
Shoubao Ma1,2, Michael A Caligiuri1,2,3, Jianhua Yu1,2,3,4
1Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Los Angeles, California.
Abstract:
Lung cancer is the leading cause of cancer-related death worldwide. Although natural killer (NK) cells are garnering interest as a potential anticancer therapy because they selectively recognize and eliminate cancer cells, their use in treating solid tumors, including lung cancer, has been limited due to impediments to their efficacy, such as their limited ability to reach tumor tissues, the reduced antitumor activity of tumor-infiltrating NK cells, and the suppressive tumor microenvironment (TME). This comprehensive review provides an in-depth analysis of the cross-talk between the lung cancer TME and NK cells. We highlight the various mechanisms used by the TME to modulate NK-cell phenotypes and limit infiltration, explore the role of the TME in limiting the antitumor activity of NK cells, and discuss the current challenges and obstacles that hinder the success of NK-cell-based immunotherapy for lung cancer. Potential opportunities and promising strategies to address these challenges have been implemented or are being developed to optimize NK-cell-based immunotherapy for lung cancer. Through critical evaluation of existing literature and emerging trends, this review provides a comprehensive outlook on the future of NK-cell-based immunotherapy for treating lung cancer.
Insights
Natural killer (NK) cells show promise for lung cancer treatment but face challenges. This review explores how the tumor microenvironment (TME) hinders NK cell therapy and discusses strategies to overcome these obstacles for improved lung cancer immunotherapy.
Area of Science:
- Immunology
- Oncology
- Cancer Research
Background:
- Lung cancer is a leading cause of cancer mortality globally.
- Natural killer (NK) cells are investigated for cancer therapy due to their cytotoxic potential.
- Therapeutic application of NK cells in solid tumors like lung cancer is limited by several factors.
Purpose of the Study:
- To analyze the intricate interactions between the lung cancer tumor microenvironment (TME) and NK cells.
- To elucidate mechanisms by which the TME impedes NK cell function and infiltration.
- To review current challenges and future strategies for optimizing NK cell-based immunotherapy in lung cancer.
Main Methods:
- Comprehensive literature review and critical evaluation of existing research.
- Analysis of mechanisms governing NK cell-TME cross-talk.
- Synthesis of emerging trends and therapeutic strategies.
Main Results:
- The TME employs various strategies to suppress NK cell infiltration and activity.
- Tumor-infiltrating NK cells exhibit reduced antitumor efficacy within the TME.
- Significant challenges exist in translating NK cell immunotherapy for lung cancer.
Conclusions:
- Understanding TME-NK cell interactions is crucial for advancing lung cancer immunotherapy.
- Developing strategies to counteract TME-mediated suppression is key to enhancing NK cell therapy efficacy.
- Optimizing NK cell-based treatments holds significant promise for improving outcomes in lung cancer patients.
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