Genetic trajectory and immune microenvironment of lung-specific oligometastatic colorectal cancer

Genetics and immunologic dynamics pushing the evolution of colorectal cancer (CRC) from the primary tumor to the metastases are largely unknown; cancer heterogeneity makes challenging both therapy and mechanistic studies. We selected patients developing CRC with lung-limited metastatic disease as only illness during their life in order to find any relevant genotype–phenotype relationship. Analysis of 523 cancer-relevant genes and of immune cells infiltration in primary and metastatic tissues revealed atypical genomic trajectories (TMB decrease, KRAS and SMAD4 regressive mutations), specific genetic events ( ERBB2 point mutations) and scarce T-cell infiltration. These insights provide novel information in oligometastatic CRC biology and new perspectives for cancer monitoring and anti-cancer therapeutic strategies.