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Poster Display session 3

1533 - Are immune checkpoint inhibitors a valid option for papillary Renal Cell Carcinoma? Transcriptomic characterization of the immune infiltrate

Date

30 Sep 2019

Session

Poster Display session 3

Topics

Tumour Site

Renal Cell Cancer

Presenters

Manon De Vries-brilland

Citation

Annals of Oncology (2019) 30 (suppl_5): v356-v402. 10.1093/annonc/mdz249

Authors

M. De Vries-brilland1, E. Menand2, V. Seegers3, J. Dauvé2, C. Passot2, J. Marion4, P. Chauvet4, A. Morel2, M. Gross-Goupil5, A. Ravaud5, E. Boughalem1, B. Escudier6, L. Albiges7

Author affiliations

  • 1 Medical Oncology, Integrative Center for Oncology, 49055 - ANGERS/FR
  • 2 Clinical Biology, Integrative Center for Oncology, 49055 - Angers/FR
  • 3 Biostatistics Department, Integrative Center for Oncology, 49055 - Angers/FR
  • 4 Laris, Université Catholique de l'Ouest, 49008 - Angers/FR
  • 5 Medical Oncology, CHU Bordeaux Hopital St. André, 33000 - Bordeaux/FR
  • 6 Medical Oncology, Gustave Roussy - Cancer Campus, 94805 - Villejuif/FR
  • 7 Medical Oncology, Institut Gustave Roussy, 94805 - Villejuif/FR

Resources

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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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