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.
Resources from the same session
5655 - Bioactivation of napabucasin triggers reactive oxygen species–mediated cancer cell death
Presenter: Fieke Froeling
Session: Poster Display session 3
Resources:
Abstract
4097 - Targeting NRG1-fusions in multiple tumour types: Afatinib as a novel potential treatment option
Presenter: Stephen V Liu
Session: Poster Display session 3
Resources:
Abstract
1129 - Aspirin and Ticagrelor for the prevention of tumour cell induced platelet aggregation
Presenter: Meera Chauhan
Session: Poster Display session 3
Resources:
Abstract
4514 - Pharmacokinetic/ pharmacodynamic (PK/PD) exposure-response characterization of GSK3359609 (GSK609) from INDUCE-1, a phase I open-label study
Presenter: Michele Maio
Session: Poster Display session 3
Resources:
Abstract
5169 - In vitro functional interrogation of viable Circulating Tumor Associated Cells (C-TACs) for evaluating Platin resistance.
Presenter: Stefan Schuster
Session: Poster Display session 3
Resources:
Abstract
5827 - Targeting ARG2 as a novel therapeutic approach for cancer
Presenter: Marcin Grzybowski
Session: Poster Display session 3
Resources:
Abstract
3129 - MPS1 and PLK1 as new therapy targets in TP53 mutated solid tumors
Presenter: Balazs Gyorffy
Session: Poster Display session 3
Resources:
Abstract
2129 - The Tumor Static Exposure (TSE) concept & utility: application to combination treatment of radiation and radiosensitizing agent in tumor xenograft experiments
Presenter: Samer El Bawab
Session: Poster Display session 3
Resources:
Abstract
1814 - General Methodology to Optimize Tumor Treating Fields Delivery Utilizing Numerical Simulations
Presenter: Noa Urman
Session: Poster Display session 3
Resources:
Abstract
3010 - The Australian Exceptional Responders Program: a National collaboration
Presenter: Megan Barnet
Session: Poster Display session 3
Resources:
Abstract