Are immune checkpoint inhibitors a valid option for papillary renal cell carcinoma? Transcriptomic characterization of the immune infiltrate
| Autor: | Pierre Chauvet, J.-M. Marion, E. Menand, Bernard Escudier, Marine Gross-Goupil, Alain Ravaud, M. de Vries-Brilland, Alain Morel, Laurence Albiges, Elouen Boughalem, J. Dauvé, Valérie Seegers, C. Passot |
|---|---|
| Přispěvatelé: | Laboratoire Angevin de Recherche en Ingénierie des Systèmes (LARIS), Université d'Angers (UA), Université Catholique de l'Ouest (UCO), Institut Bergonié [Bordeaux], UNICANCER, Hôpital Saint-André, Département de radiothérapie [Gustave Roussy], Institut Gustave Roussy (IGR), Association Française d'Urologie, Département de médecine oncologique [Gustave Roussy], Institut Bergonié - CRLCC Bordeaux |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Immune checkpoint inhibitors [SDV]Life Sciences [q-bio] Population education Immune markers Officer 03 medical and health sciences 0302 clinical medicine Immune infiltration Cancer genome medicine health care economics and organizations Immune infiltrate education.field_of_study Training set business.industry Hematology 3. Good health 030104 developmental biology Oncology 030220 oncology & carcinogenesis Family medicine business |
| Zdroj: | Annals of Oncology Annals of Oncology, Elsevier, 2019, 30, pp.v392-v393. ⟨10.1093/annonc/mdz249.066⟩ Annals of Oncology, Oxford University Press (OUP), 2019, 30, pp.v392-v393. ⟨10.1093/annonc/mdz249.066⟩ |
| ISSN: | 0923-7534 1569-8041 |
| DOI: | 10.1093/annonc/mdz249.066⟩ |
| Popis: | 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. 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|