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We identified 34 immunogenomic interactions (IGXs) linking cancer drivers and immune cells to patient survival across 13 cancer types. These findings reveal prognostic biomarkers and therapeutic targets by integrating genomic and immune data.

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Area of Science:

  • Oncology
  • Immunology
  • Genomics

Background:

  • Cancer progression is influenced by somatic genomic alterations and the tumor immune microenvironment (TME).
  • The interplay between genomic drivers and TME features in shaping tumor evolution and clinical outcomes is not fully understood.

Purpose of the Study:

  • To develop a framework for integrating multi-omics data to identify interactions between cancer drivers and TME characteristics associated with clinical outcomes.
  • To discover novel immunogenomic interactions (IGXs) with prognostic potential.

Main Methods:

  • Developed the multi-omics analysis framework PACIFIC.
  • Systematically integrated genetic cancer drivers and immune cell infiltration profiles.
  • Analyzed 8500 primary tumor samples across 26 cancer types.

Main Results:

  • Identified 34 IGXs in 13 cancer types, linking specific genomic alterations and immune cell levels to patient survival.
  • Found that IGXs can define tumor subsets with distinct immunogenicity and immunotherapy target gene expression.
  • Observed an IGX in luminal-A breast cancer (MEN1 deletion and low neutrophils) associated with poorer progression-free survival.

Conclusions:

  • The PACIFIC framework effectively integrates multi-omics and clinical data to identify clinically relevant IGXs.
  • Discovered prognostic IGXs that offer hypotheses for mechanistic studies, biomarker development, and therapeutic targeting.
  • Co-occurrence patterns of cancer drivers and TME characteristics reveal synergistic interactions with prognostic value.