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
4235 - First results of safety profile of nivolumab (NIVO) in combination with stereotactic body radiotherapy (SBRT) in II and III line of patients (pts) with metastatic renal cell carcinoma (mRCC) in NIVES Study
Presenter: Cristina Masini
Session: Poster Display session 3
Resources:
Abstract
2262 - Real world experience of Nivolumab therapy in Metastatic Renal Cancer patients: a 3 year multi-centre review
Presenter: Joanna Hack
Session: Poster Display session 3
Resources:
Abstract
4441 - “A pilot study of tremelimumab (treme) with or without cryoablation (cryo) in patients (pts) in metastatic renal cell carcinoma (mRCC).”
Presenter: Matthew Campbell
Session: Poster Display session 3
Resources:
Abstract
2613 - Lenvatinib (Len) alone or in combination with Everolimus (Eve) in heavily pretreated patients (pts) with metastatic renal cell carcinoma (mRCC) after immune checkpoint inhibitors (ICI) and VEGFR-targeted therapies: A single-institution experience
Presenter: Andrew Wiele
Session: Poster Display session 3
Resources:
Abstract
3249 - Weight loss is an underestimated adverse event with cabozantinib in patients with metastastic renal cell carcinoma (mRCC).
Presenter: Emeline Colomba
Session: Poster Display session 3
Resources:
Abstract
2405 - Impact of corticosteroids on nivolumab activity in metastatic clear cell renal cell carcinoma.
Presenter: Felix Lefort
Session: Poster Display session 3
Resources:
Abstract
4020 - Skeletal muscle loss as an adverse event during Cabozantinib treatment in patients with metastatic renal cell carcinoma
Presenter: Carolina Alves Costa Silva
Session: Poster Display session 3
Resources:
Abstract
2407 - Long term relative survival (RS) in patients with primary metastatic kidney cancer (primary mRCC): an analysis of 2,167 patients from the Austrian National Cancer Registry (ANCR).
Presenter: Monika Hackl
Session: Poster Display session 3
Resources:
Abstract
2470 - Advanced renal cell carcinoma: first results from the prospective research platform CARAT for patients with mRCC in Germany
Presenter: Peter Goebell
Session: Poster Display session 3
Resources:
Abstract
3367 - Treatment-Free Survival, With and Without Toxicity, as a Novel Outcome Applied to Immuno-Oncology Agents in Advanced Renal Cell Carcinoma
Presenter: Meredith Regan
Session: Poster Display session 3
Resources:
Abstract