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Review
. 2025 Feb;17(2):133-145.
doi: 10.1080/1750743X.2025.2460965. Epub 2025 Feb 5.

From natural defenders to therapeutic warriors: NK cells in HIV immunotherapy

Thessa Laeremans  1 , Amber Janssens  1 , Joeri L Aerts  1
Affiliations
Review

From natural defenders to therapeutic warriors: NK cells in HIV immunotherapy

Thessa Laeremans et al. Immunotherapy. 2025 Feb.

Abstract

Cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells both play essential roles in controlling viral infections by eliminating virus-infected cells. Unlike CTLs, which require priming and activation by antigen-presenting cells, NK cells possess a remarkable capacity to mount a rapid antiviral immune response immediately after infection. Additionally, they can bolster the adaptive immune system by secreting cytokines and directly interacting with other immune cells. However, during chronic human immunodeficiency virus (HIV) infection, various immune cells, including NK cells, experience functional impairments. This has led to the exploration of NK cell-based immunotherapy as a promising strategy to reverse these dysfunctions and contribute to the pursuit of a functional cure for HIV. Building on the success of NK cell therapies in cancer treatment, these approaches offer significant potential for transforming the HIV cure field. This review provides a comprehensive overview of the latest advances in NK cell-based immunotherapy for HIV, outlining the progress made and the key challenges that must be overcome to achieve a functional cure for people living with HIV.

Keywords: ADCC; CAR NK cells; HIV; functional cure; immunotherapy; memory NK cells; natural killer cells.

Plain language summary

The immune system is essential for fighting off viral infections, including HIV. Different types of immune cells work together, each playing its own role in this process. One important type is natural killer (NK) cells, which can react quickly to infections and help kickstart other immune responses. In people living with HIV, these NK cells lose some of their effectiveness over time because of the ongoing nature of the infection. Scientists are looking into ways to boost NK cell function through therapies to help in the quest for an HIV cure. Since these treatments have already been successful in fighting cancer, there is hope they could also be effective against HIV. Still, there are challenges that need to be solved before achieving a lasting cure for the virus.

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Conflict of interest statement

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties

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