Renee Maria Saliby: Immunogenomic determinants of exceptional response to ICI in renal cell carcinoma
Renee Maria Saliby, Postdoctoral GU Oncology Research Fellow at Dana-Farber Cancer Institute, shared on X:
“Excited to share our latest study published in Nature Cancer co-led with amazing co-first authors and friends Tejas Jammihal and Chris Labaki under the exceptional mentorship of Toni Choueiri, David Braun, Sachet Ashok Shukla.
We analyzed genomic and transcriptomic data from RCC patients treated with IO+IO (PD-1/CTLA-4 inhibitors) or IO+VEGF (PD-L1/VEGF inhibitors). Our goal? To uncover how IO-based regimens achieve exceptional -deep and durable- responses in a subset of patients with renal cell carcinoma (RCC).
We performed WES +/- RNA-seq on tumor samples from patients enrolled in the CheckMate 214 and JAVELIN Renal 101 trials. Exceptional responses (ER) were defined as:
Complete response (CR) & ≥12mo PFS
Partial response (PR) + ≥50% tumor shrinkage & ≥24mo PFS.
Any PR with ≥36mo PFS
Exceptional responses to IO+IO regimens were associated with higher clonal neoantigen load (CNL), which may drive robust cytotoxic T-cell responses within the tumor. Notably, tumor mutational burden (TMB) was not associated with ERs in these regimens.
For IO+VEGF regimens, exceptional responses were achieved in tumors that were enriched with tertiary lymphoid structures (TLS), adaptive immunity hubs that promote B-cell activity and humoral immune responses.
In IO+VEGF regimens and tumors with low TLS signatures, exceptional responses were achieved through upregulated metabolic pathways, including cholesterol and fatty acid metabolism.
Our work provides a molecular framework to understand how some patients with metastatic RCC benefit from an exceptional response to IO-based regimens, offering paths to optimize therapy.
This work wouldn’t be possible without the courage of patients, the support of their families, and the dedication of our collaborators across academia and industry.”
Authors: Tejas Jammihal, Renee Maria Saliby, Chris Labaki, et al.
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