A machine learning-derived gene signature that integrates germline HLA characteristics with a distinct spatial community of CD8+ T cells and tumor-associated macrophages showing immunogenic interactions is predictive of the response to immunotherapy in patients with advanced kidney cancer.
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References
Saliby, R. M. et al. Update on biomarkers in renal cell carcinoma. Am. Soc. Clin. Oncol. Educ. Book 44, e430734 (2024). This comprehensive review article highlights the current state of the art on biomarkers in RCC.
Saliby, R. M. et al. Impact of renal cell carcinoma molecular subtypes on immunotherapy and targeted therapy outcomes. Cancer Cell 42, 732–735 (2024). This recent paper reports on various molecular subtypes in RCC and demonstrates the challenges of cross-study validation of current biomarkers for immunotherapy.
Naulaerts, S. et al. Multiomics and spatial mapping characterizes human CD8+ T cell states in cancer. Sci. Transl. Med. 15, eadd1016 (2023). This paper reports on clinically relevant states of CD8+ T cells mapped via an integrative multi-omics and spatial biomarker framework.
Sprooten, J. et al. Lymph node and tumor-associated PD-L1+ macrophages antagonize dendritic cell vaccines by suppressing CD8+ T cells. Cell Rep. Med. 5, 101377 (2024). This paper provides proof of concept for the use of reverse translation to reveal novel immunotherapy-resistance mechanisms and vaccine formulations relevant for T cell-depleted tumors.
Manczinger, M. et al. Negative trade-off between neoantigen repertoire breadth and the specificity of HLA-I molecules shapes antitumor immunity. Nat. Cancer 2, 950–961 (2021). This paper reports the impact of specificity in the neo-antigen presentation of an HLA repertoire in the context of response to immunotherapy.
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This is a summary of: Kinget, L. et al. A spatial architecture-embedding HLA signature to predict clinical response to immunotherapy in renal cell carcinoma. Nat. Med. https://doi.org/10.1038/s41591-024-02978-9 (2024).
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Heritable and spatial immunogenic traits co-predict the efficacy of immunotherapy in kidney cancer. Nat Med 30, 1537–1538 (2024). https://doi.org/10.1038/s41591-024-03020-8
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DOI: https://doi.org/10.1038/s41591-024-03020-8
