Abstract 1533
Background
Papillary Renal Cell Carcinoma (pRCC) is the most common non-clear cell RCC (nccRCC). Pivotal studies evaluating immune checkpoint inhibitors mostly excluded nccRCC. PD-1/PD-L1 inhibitors exhibit limited activity in metastatic pRCC. The immune microenvironment in pRCC is unknown.
Methods
In silico, we studied the expression of cytotoxic lymphocyte infiltration (CYT), using a descriptive (by CIBERSORT) and specific quantitative approach, as well as the expression of inhibitors checkpoint immune markers (ICI), in 258 localized papillary renal cell tumors using RNA-seq data from The Cancer Genome Atlas (TCGA) as training set. Based on previous report, we selected 8 genes of interest (CD8a, CD8b, GZMA, PRF1, PD1, PDL1, PDL2 and CTLA4). An independent data set of 34 localized pRCC (gene expression) was used as a validation set.
Results
Using a clustering method based on the expression level of 8 predefined genes of interest, we identified 3 groups, differentiated by CYT and ICI expression. In validation cohort, we observed similar clustering. Cluster 3, characterized by a CYT and ICI high expression, was significantly associated with increased population of TCD8, TCD4 helper, M1 macrophages and dendritic cells in CIBERSORT analysis. Additionally, these immune clusters were not associated with indels neo-antigen load but were significantly correlated with the MHC class I antigen presenting machinery expression (APM) (p = 1.1.10-11) and interferon-gamma gene expression (p = 1.6.10-13).
Conclusions
We characterized cytotoxic immune infiltration in pRCCs. Cluster 3 could correspond to a population of immunotherapy responders. Transcriptomic immune signature validation in pRCCs patients treated with immunotherapy is warranted.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Manon de Vries-Brilland.
Funding
Has not received any funding.
Disclosure
M. Gross-Goupil: Honoraria (institution), Advisory / Consultancy: Ipsen; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution): Janssen; Honoraria (institution), Advisory / Consultancy: Astellas; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: MSD; Research grant / Funding (institution): BMS; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution), Travel / Accommodation / Expenses: Pfizer; Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Travel / Accommodation / Expenses: Sanofi; Travel / Accommodation / Expenses: Amgen. A. Ravaud: Research grant / Funding (institution), Travel / Accommodation / Expenses, Officer / Board of Directors: Pfizer; Travel / Accommodation / Expenses, Officer / Board of Directors: BMS; Travel / Accommodation / Expenses, Officer / Board of Directors: AstraZeneca; Travel / Accommodation / Expenses, Officer / Board of Directors: Roche; Travel / Accommodation / Expenses, Officer / Board of Directors: MSD; Travel / Accommodation / Expenses, Officer / Board of Directors: Ipsen. B. Escudier: Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: BMS; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Pfizer; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy, Research grant / Funding (self): Aveo; Advisory / Consultancy: Ipsen; Advisory / Consultancy: Roche; Advisory / Consultancy: EUSA. L. Albiges: Advisory / Consultancy: Pfizer; Advisory / Consultancy: Novartis; Advisory / Consultancy: BMS; Advisory / Consultancy: Ipsen; Advisory / Consultancy: Roche; Advisory / Consultancy: MSD; Advisory / Consultancy: AstraZeneca. All other authors have declared no conflicts of interest.
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