Interplay of somatic alterations and immune infiltration modulates response to PD-1 blockade in advanced clear cell renal cell carcinoma

Copy-Number Alteration Burden Differentially Impacts Immune Profiles and Molecular Features of Hepatocellular Carcinoma

“…In terms of focal events, our FS correlated significantly with the Immune score in 12 out of 27 tumor types, but HCC was not among them ( Figure 1B and 1D). This places HCC in the subset of tumors were broad aneuploidy events adversely affect immune cell action against tumors [12], but also corroborates that the relation between immunity and CNA alterations is not universal across cancer types, highlighting the importance of considering the tumor specific context [15][16][17][18].…”

“…Recently, pancancer studies have described broad and focal CNA burdens as genomic features able to determine tumor immune infiltration and immune exclusion in several cancer types [12,15]. Notably, the strength and direction of this immunogenomic correlations may not be common in all cancer types [16][17][18], mainly due to the different context of each tumor [43,44]. The impact of CNAs in the setting of HCC has not been comprehensively addressed.…”

“…Author Manuscript Published OnlineFirst on September 1, 2020; DOI: 10.1158/1078-0432.CCR- universal in all cancer types [15][16][17][18], underlining the need to investigate the impact of aneuploidy considering the tumor tissue-specific context.…”

Tumor-infiltrating TNFRSF9 + CD8 + T cells define different subsets of clear cell renal cell carcinoma with prognosis and immunotherapeutic response

“…The role of TNFRSF9 + CD8 + T cells in response to ICB was analyzed in public datasets of ccRCC and melanoma from Braun et al and Riaz et al, 25,26 respectively. In the ccRCC cohort from Braun et al, higher TNFRSF9 + CD8 + T cells signature was associated with higher max tumor size shrinkage in nivolumab treatment arm ( Figure 5(a) left, r= −0.448, p= .003) but not everolimus treatment arm ( Figure 5(a) right, r= 0.155, p= .397).…”

In the literature: August 2020

“…Recently, a very interesting article has been published in Nature Medicine by Braun et al, 2 trying to answer several questions regarding the relation of molecular alterations and response to ICI in ccRCC. The authors performed an integrated genomic, transcriptomic and immunopathologic analysis of advanced-stage ccRCC tumours derived from 592 patients enrolled in three prospective clinical trials of PD-1 blockade to evaluate the landscape of somatic alterations, copy number changes, the patterns of immune infiltration and the clinical outcome to PD-1 blockade.…”