Immuno-oncology

Oral

Correlation of Cancer Pathways and Mutational Load with Immunephenotype Pan Cancer

Friday, June 16
6:15 PM - 7:30 PM

Further advances in the revolution that cancer immunotherapy is providing are hampered by a lack of understanding of the underlying genetics determining the pre-treatment tumor immune environment. Consensus clustering on 32 TCGA cancer datasets consisting of 9219 samples, was performed using an immune signature consisting of a combination of Th1 orienting genes and regulatory immune genes that associates with improved prognosis. A high degree of correlation was found between these genes across the different cancer sets. In order to elucidate the mechanisms underlying the unfavorable, non-inflamed tumor phenotype we investigated the tumor load and inverse correlations between this signature and a large set of published cancer pathways. The Th1 phenotype was associated with higher number of mutations in some but not all tumors. This association was especially evident in cancers where micro satellite instability plays a role. However, this association cannot explain the difference in immune phenotype on its own. We recently showed the association of MAPK pathway perturbations, originating from MAP3K1 or MAP2K4 mutations, with a poor immune phenotype in breast cancer and are now trying to identify other pathways that associate pan-cancer with the unfavorable phenotype. Inversely correlating pathways are the WNT/B-Catenin, Hedgehog and KRAS signaling. The inverse correlation of some other pathways involved in DNA repair, G2M checkpoint or mismatch repair can be associated with the increase in mutational load observed in these samples before. Therapeutic targeting of these pathways might expand the patient cohort responsive to immunotherapy and needs further in-vitro and in-vivo experimentation.


Wouter Hendrickx

Postdoctoral Fellow
Sidra Medical and Research Center

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    Cristina Maccalli

    Sidra Medical and Research Center

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      Jessica Roelands

      PhD candidate
      Sidra Medical and Research Center

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        Darawan Rinchai

        Postdoctoral Fellow
        Sidra Medical and Research Center

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          Michele Ceccarelli

          Qatar Foundation

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            Davide Bedognetti

            Sidra Medical and Research Center

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              Correlation of Cancer Pathways and Mutational Load with Immunephenotype Pan Cancer



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