Publications by authors named "Tyler J Aprati"
Article Synopsis
- The introduction of immune checkpoint blockade (ICB) has greatly improved treatment outcomes for advanced melanoma, but many patients still become resistant to it due to unclear reasons.
- Although combining different ICB therapies has been shown to enhance response rates, it also comes with increased toxicity for patients.
- An analysis of tumor samples from ICB-naïve patients revealed that high genomic heterogeneity and low ploidy can identify those who are intrinsically resistant to aPD-1, leading to a predictive model that may help tailor treatment strategies.
While immune-checkpoint blockade (ICB) has revolutionized treatment of metastatic melanoma over the last decade, the identification of broadly applicable robust biomarkers has been challenging, driven in large part by the heterogeneity of ICB regimens and patient and tumor characteristics. To disentangle these features, we performed a standardized meta-analysis of eight cohorts of patients treated with anti-PD-1 (n=290), anti-CTLA-4 (n=175), and combination anti-PD-1/anti-CTLA-4 (n=51) with RNA sequencing of pre-treatment tumor and clinical annotations. Stratifying by immune-high vs -low tumors, we found that surprisingly, high immune infiltrate was a biomarker for response to combination ICB, but not anti-PD-1 alone.
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- Researchers are merging unstructured patient data with structured health records to create the MSK-CHORD dataset, consisting of varied cancer types from nearly 25,000 patients at Memorial Sloan Kettering Cancer Center.
- This dataset allows for in-depth analysis of cancer outcomes using advanced techniques like natural language processing, revealing new relationships that smaller datasets may not show.
- Using MSK-CHORD for machine learning models, findings suggest that incorporating features from these unstructured texts can better predict patient survival than relying solely on genomic data or cancer staging.
Liver metastasis (LM) confers poor survival and therapy resistance across cancer types, but the mechanisms of liver-metastatic organotropism remain unknown. Here, through in vivo CRISPR-Cas9 screens, we found that Pip4k2c loss conferred LM but had no impact on lung metastasis or primary tumor growth. Pip4k2c-deficient cells were hypersensitized to insulin-mediated PI3K/AKT signaling and exploited the insulin-rich liver milieu for organ-specific metastasis.
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