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Natural killer cell-based immunotherapies for colorectal cancer: Current strategies, challenges, and future

Xiao-Jun Zhang1, Yan Yu1, Jing-Yu Li2

  • 1Department of Clinical Laboratory, Honghui Hospital, Xi'an Jiaotong University, Xi'an 710054, Shaanxi Province, China.

World Journal of Gastroenterology
|September 12, 2025
PubMed

Insights

Natural killer (NK) cell immunotherapy shows great promise for colorectal cancer treatment. This review details NK cell approaches, challenges, and future strategies for enhanced efficacy.

Area of Science:

  • Immunology
  • Oncology
  • Cancer Therapy

Background:

  • Natural killer (NK) cells possess inherent anti-tumor capabilities, making them attractive for colorectal cancer (CRC) treatment.
  • NK cell-based immunotherapies offer a promising avenue for targeting CRC without prior sensitization.

Purpose of the Study:

  • To comprehensively review NK cell-based immunotherapeutic strategies for colorectal cancer.
  • To highlight the clinical potential, limitations, and challenges associated with NK cell therapy in CRC.
  • To explore innovative approaches for overcoming current barriers in NK cell immunotherapy.

Main Methods:

  • Review of existing literature on NK cell-based immunotherapies for colorectal cancer.
  • Examination of various approaches including cytokine therapy, immune checkpoint inhibition, ADCC, and adoptive cell transfer.
  • Discussion of challenges in NK cell expansion, genetic engineering (CAR-NK), and tumor microenvironment (TME) modulation.

Main Results:

  • NK cell therapies demonstrate potential in recognizing and eliminating CRC cells.
  • Current limitations include challenges in NK cell expansion, genetic engineering, and overcoming TME-mediated immunosuppression.
  • Innovative strategies like combination therapies, nanotechnology, and personalized medicine are being explored.

Conclusions:

  • NK cell immunotherapy is a transformative modality for colorectal cancer treatment.
  • Standardized manufacturing, improved NK cell persistence, and clinical validation are crucial for future development.
  • Overcoming current barriers through innovative strategies is key to realizing the full potential of NK cell therapy.
Keywords:
Colorectal cancerImmunosuppressionImmunotherapyNatural killer cellsTumor microenvironment

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