Analytic pipelines to assess the relationship between immune response and germline genetics in human tumors

Sayaman, Rosalyn W.; Saad, Mohamad; Heimann, Carolina; Hu, Donglei; Kunji, Khalid; Roelands, Jessica; Wolf, Denise M.; Huntsman, Scott; Ceccarelli, Michele; Thórsson, Vésteinn; Ziv, Elad; Bedognetti, Davide

doi:10.1016/j.xpro.2022.101809

Cited by 2 publications

(1 citation statement)

References 30 publications

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“…Immune traits considered for analysis were based on a collection of well-characterized immune traits 3 , 72 . This collection includes 68 gene signatures related to immunomodulatory signaling, including IFN signaling, TGF-β, wound healing (core serum response) and T cell/B cell response 3 , 73 . Gene expression values were median centered and gene symbols were mapped to EntrezIDs (org.Hs.eg.db_3.6.0).…”

Section: Methodsmentioning

confidence: 99%

An integrated tumor, immune and microbiome atlas of colon cancer

Roelands

Kuppen

Ahmed

et al. 2023

Nat Med

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The lack of multi-omics cancer datasets with extensive follow-up information hinders the identification of accurate biomarkers of clinical outcome. In this cohort study, we performed comprehensive genomic analyses on fresh-frozen samples from 348 patients affected by primary colon cancer, encompassing RNA, whole-exome, deep T cell receptor and 16S bacterial rRNA gene sequencing on tumor and matched healthy colon tissue, complemented with tumor whole-genome sequencing for further microbiome characterization. A type 1 helper T cell, cytotoxic, gene expression signature, called Immunologic Constant of Rejection, captured the presence of clonally expanded, tumor-enriched T cell clones and outperformed conventional prognostic molecular biomarkers, such as the consensus molecular subtype and the microsatellite instability classifications. Quantification of genetic immunoediting, defined as a lower number of neoantigens than expected, further refined its prognostic value. We identified a microbiome signature, driven by Ruminococcus bromii, associated with a favorable outcome. By combining microbiome signature and Immunologic Constant of Rejection, we developed and validated a composite score (mICRoScore), which identifies a group of patients with excellent survival probability. The publicly available multi-omics dataset provides a resource for better understanding colon cancer biology that could facilitate the discovery of personalized therapeutic approaches.

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