Lack of T-cell infiltration is the main mechanism of primary resistance to checkpoint blockade therapies. Here, we performed a transcriptomic analysis of metastatic melanoma biopsies taken from patients treated with… Click to show full abstract
Lack of T-cell infiltration is the main mechanism of primary resistance to checkpoint blockade therapies. Here, we performed a transcriptomic analysis of metastatic melanoma biopsies taken from patients treated with anti-PD1 (n=23) with biopsies pre- (n=17) and during treatment (n=22), and investigated cancer cell intrinsic mechanisms of immune evasion. We classified our samples based on their T-cell infiltration status using a validated set of immune genes for T-cell infiltration (Spranger et al., 2015), normalized within gene and scored the samples from 0 (least infiltrated) to 1 (most infiltrated). In order to identify genes that anti-correlate with infiltration, we performed differential gene expression analysis between non-infiltrated (n= 18) and infiltrated tumors (n=21) regardless clinical response and condition. The analysis resulted in total of 1904 genes enriched in the non-infiltrated group (log2foldchange > 1, q-value Citation Format: Gabriel Abril-Rodriguez, Catherine S. Grasso, Jesse M. Zaretsky, Beata Berent-Maoz, Siwen Hu-Lieskovan, Antoni Ribas. Role of PAK4 in cancer immune cell exclusion [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4755.
               
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