The immune cells PD-L1 staining was not selected in the final model but it was borderline significant in the contrast comparing IC0 vs IC2+ ( p = 0.054), indicating its potential clinical relevance for those patients with the highest percentage of stained immune cells (IC2+) as compared with IC0.
A number of hallmark pathways were found significantly up or downregulated when comparing the RB1 and TP53 concurrently altered samples with the DWT tumors at a FDR < 0.10 (Table 1 ). A highly significant upregulation of pathways related to cell proliferation and cell division was clearly apparent (Mitotic spindle, G2M checkpoint, E2F targets and MYC targets) and expected in the RB1 and TP53 altered samples.
These results do not allow us to assume that RB1 HD are a priori less sensitive to ICIs than the other RB1 mutants, as the RB1 HD have a higher (and almost statistically significant) average TMB and a significantly higher neoantigen load than the rest of the RB1 mutants as a whole, even though RB1 HD also have a lower relative infiltration of immunity relevant cell populations and their signaling (cytotoxic lymphocytes, NK cells, B cells, the monocytic lineage, the T cell inflamed signature and the cytolysis signature) than the rest of RB1 mutants when they are both compared separately with RB1 WT samples (please see the first section of the Results).