65 Sex-Dependent NK-Cell Immunosurveillance and Control of ccRCC Liver Metastasis

Q: What does this research mean for the field?

Female-intrinsic factors prime natural killer (NK) cell populations for enhanced tumor immune surveillance, conferring protection against clear cell renal cell carcinoma (ccRCC) liver metastasis. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.ESTABLISHES_NEW_DIRECTION.

Doris Zheng; Hui Jiang; Nicole Rittenhouse; Fengshen Kuo; Rebecca Sager; Amrita Nargund Mangalvedhekar; Jing Zhang; Daniel Barbakoff; Yash Khandwala; Peng Li; Liang Liang Ji; David Solit; A Ari Hakimi; Lynda Vuong

doi:10.1093/oncolo/oyag312.066

September 1, 2026The OncologistOpen Access

65 Sex-Dependent NK-Cell Immunosurveillance and Control of ccRCC Liver Metastasis

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Key Points

To determine how innate immune mechanisms, specifically natural killer cells, drive sex disparities and protect against clear cell renal cell carcinoma progression and liver metastasis.
Evaluated primary and metastatic tumor growth in immunocompetent, immune-deficient, and genetically engineered mouse models using checkpoint blockade-resistant (VpRM) and responsive (VCCB) renal cell carcinoma subtypes.
Conducted antibody-mediated depletion of CD4+ T-cells, CD8+ T-cells, B-cells, NK cells, and group 1 innate lymphoid cells to identify immune mediators of sex-biased metastasis.
Used bone marrow chimera models transferring male and female donor cells into sex-matched and mismatched hosts to differentiate hematopoietic from non-hematopoietic drivers of protection.
In immunocompetent mice, females demonstrated smaller primary tumors and near-complete protection from VpRM liver metastases compared to males, an effect reversed in immunocompromised settings.
Female livers showed higher infiltration of mature, cytotoxic natural killer cells and group 1 innate lymphoid cells expressing elevated levels of granzyme B and C.
Depleting natural killer cells selectively eliminated the female protection against liver metastases in both wild-type and Rag1-deficient mice, while bone marrow chimeras confirmed that both host-extrinsic and NK-intrinsic female factors sustain surveillance.

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Implication

Preclinical study reveals sex-biased natural killer cell immunosurveillance protects against renal cell carcinoma liver metastases in female mice, highlighting innate immunity as a key survival...

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Cite This Study

Zheng et al. (2026) studied this question.

synapsesocial.com/papers/6a993635636c6408cfa7f179 https://doi.org/10.1093/oncolo/oyag312.066

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65 Sex-Dependent NK-Cell Immunosurveillance and Control of ccRCC Liver Metastasis

Key Points

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Cite This Study

65 Sex-Dependent NK-Cell Immunosurveillance and Control of ccRCC Liver Metastasis

Key Points

No abstract yet

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Implication

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Cite This Study

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