A Multimodal Framework to Guide Solid Tumor Indications for Natural Killer Cell-Based Therapy

Our plain-English summary of A Multimodal Framework to Guide Solid Tumor Indications for Natural Killer Cell-Based Therapy, by L. Chiossone, V. Picant, Q. Barbier, et al (European Journal of Immunology, 2026).

The study

• Authors: L. Chiossone, V. Picant, Q. Barbier, T.A. Fehniger, E. Vivier
• Journal: European Journal of Immunology
• Published: 2026;56(9):e70283
• Type of article: Systematic review
• Read it: PubMed · Publisher · Free full text

Abstract

T cell-based immunotherapies have achieved remarkable success in hematological malignancies but remain limited in solid tumors. Natural killer (NK) cells offer a compelling complementary approach, given their ability to recognize and kill tumor cells independently of neoantigen presentation and MHC class I expression. This study integrates multiomic analyses, clinical trial data, and transcriptomic analyses to systematically identify solid tumor indications most likely to benefit from NK cell-based therapies. Immunohistochemical analysis revealed that NK cells infiltrate multiple tumor types, with the highest abundance in kidney tumors. Systematic review of 177 clinical trials identified variable efficacy across solid tumor indications, without a clearly superior tumor type or intervention. Transcriptomic profiling of over 10,000 TCGA samples assessed NK cell infiltration, cytotoxic fitness, and tumor microenvironment composition, highlighting kidney renal cell carcinoma, lung adenocarcinoma and squamous cell carcinoma, cervical and endocervical cancers, and mesothelioma as promising candidates for future clinical evaluation. Together, these findings provide a multimodal framework to prioritize tumor indications and improve the rational design of future NK cell clinical trials.

© 2026 The Author(s). European Journal of Immunology published by Wiley‐VCH GmbH.

In plain English

This article, labeled a review, combined three sources of information to suggest which solid tumors might suit treatments based on natural killer (NK) cells, a type of immune cell. First, the authors analyzed tissue staining data from an earlier study of lung, pancreas, gastric, kidney, colon, head and neck, and liver tumors. NK cells were found in all seven tumor types, most often in kidney tumors. Second, they searched ClinicalTrials.gov for trials of NK cell infusions in solid tumors started between January 2000 and June 2025, keeping 177 of 807 trials. Efficacy results were found for 49. Responses varied widely, and no tumor type or treatment could be clearly identified as superior. Third, they analyzed gene activity data from more than 10,000 tumor samples covering 31 cancer types. The authors concluded that kidney renal clear cell carcinoma, lung adenocarcinoma and squamous cell carcinoma, cervical and endocervical cancers, and mesothelioma showed the most favorable biology for NK cell activity. They cautioned that the gene activity analyses are limited by differences between tumor samples. The article does not mention asbestos.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Review (published as 'Highlights-reviews') combining analysis of previously generated immunohistochemistry data, a search of a clinical trial registry, and analysis of tumor gene-expression (RNA-seq) data from the TCGA database
• Who was studied: Three data sets: (1) tumor tissue samples of seven types (lung, pancreas, gastric, kidney, colon, head and neck, liver) from immunohistochemistry data generated in an earlier study; (2) 177 clinical trials of NK cell infusions in solid tumors started from January 1, 2000 to June 30, 2025, retained from 807 found on ClinicalTrials.gov; (3) more than 10,000 tumor samples covering 31 cancer types in the TCGA database
• Exposure: No asbestos exposure was studied. The subject was NK cell-based therapies and NK cell presence in tumors. In the clinical trials, 83 used NK cells alone and 94 combined them with chemotherapy, cytokines (mainly IL-2 or IL-15), or antibodies.
• Main results:
  • In the tissue staining data (seven tumor types), NK cells were detected in all tumor types, with the highest detection rate in kidney tumors
  • Of the 177 trials, 114 used NK cells that were not genetically modified, 53 used CAR-NK cells, and 10 used the NK-92 cell line
  • Efficacy results, expressed as overall response rate, were found for 49 of the trials
  • Across the trials with efficacy results, no single tumor type or intervention could be clearly identified as giving superior clinical benefit
  • In the TCGA gene-expression analysis, a group of tumors showed microenvironment features favorable to NK cell killing: kidney renal clear cell carcinoma, lung adenocarcinoma and squamous cell carcinoma, mesothelioma, pancreatic adenocarcinoma, cervical and endocervical cancers, head and neck squamous cell carcinoma, bladder urothelial carcinoma and sarcoma
  • Lung, kidney, cervical and endocervical cancers and mesothelioma also showed substantial infiltration by functional NK cells in the TCGA data
  • Expression of chemokines that recruit NK cells showed no major differences among the tumor types
• The authors' conclusion: The authors concluded that kidney renal clear cell carcinoma, lung adenocarcinoma and squamous cell carcinoma, cervical and endocervical cancers, and mesothelioma present the most favorable biological landscape for NK cell-mediated antitumor activity and may be promising candidates for NK cell-based therapies
• Limitations the authors state:
  • The tumor-type conclusions rest on bulk transcriptomic analyses, which are limited by differences between tumor samples in immune cell infiltration, tumor stage and prior treatments
  • Few clinical trials reported efficacy outcomes for each tumor type
  • Variability in trial responses may reflect differences in the prior treatments patients received before NK cell infusion
  • The findings still need prospective validation in dedicated clinical trials

Topics

Medical terms in this study, explained in our Lexicon: Clinical Trial, Systematic Review, Tumor Microenvironment, Carcinoma, Lung Adenocarcinoma, Squamous Cell Carcinoma, Mesothelioma.

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