Laboratory for Immunomonitoring in Oncology (L.I.O)

Activities

The Laboratory of Immunomonitoring in Oncology (LIO), created at the end of 2014, is a translational research unit. The main objective of the laboratory is to identify blood or tumor biomarkers that can predict the response or resistance to anti-tumor immunotherapies, as well as the emergence of some immunological adverse effects that may be linked to these treatments. Another objective is to understand the mechanisms of action of anti-tumor immunotherapies.

The LIO is specialized in the evaluation of immunological profiles and the functional analysis of lymphocyte subpopulations in real-time in fresh samples. We monitor and characterize the immune responses following the administration of immunomodulatory therapeutic products (antibodies blocking immune checkpoints, agonist monoclonal antibodies, cytokines, etc.) in cancer patients.

In collaboration with industrial partners, the LIO is involved in the preclinical evaluation of immunotherapies in order to understand their mechanism of action, but also to predict the most effective therapeutic combinations to treat patients.

Skills and expertise

The LIO has developed and validated a standardized 10-color cytometry using lyophilized panels (DuraClone®, Beckman Coulter), making it possible to quantitatively and qualitatively monitor most populations of the immune system in the context of clinical trials in whole blood samples or fresh tissue biopsies.

The LIO performs functional tests for ex-vivo re-stimulation of PBMCs or lymphocytes infiltrating tumors.

The LIO has developed expertise in the analysis of innovative immunotherapies in preclinical murine models under scientific contracts with industry.

In addition, the LIO is developing its own research projects in order to better understand the functional role of some immune populations in the efficacy or resistance to anti-tumor immunotherapies.

Services provided

• Phenotypic characterization of different immune populations in blood, PBMCs and tumor tissues
• Functional characterization of different immune populations
• Multiplex quantification of soluble factors in plasma, serum and culture supernatants
• Flow cytometry data analysis
• Custom interpretation of experimental data according to requests from academic or industrial collaborators
• Development of new cytometry panels (up to 13 colors) and functional tests in collaboration with project leaders
• Advice on antitumor immunology
• Advice on the development of research projects on anti-tumor immunotherapy

Equipments

• 1 MACSQuant 16 Cytometer – Miltenyi Biotec Inc.
• 1 CytoFLEX S base Cytometer – Beckman Coulter
• 2 GALLIOS Cytometer – Beckman Coulter
• MAGPIX Multiplexing System – Luminex B.V.
• MESO QuickPlex SQ 120 – Meso Scale Discovery (LRTI)
• GentleMACS Dissociator - Miltenyi Biotec Inc.
• Vi-CELL XR Cell Analyzer – Beckman Coulter
• xCELLigence RTCA - Agilent

Lab members

Lab head
Prof. Nathalie Chaput-Gras
Email

Lab manager
Dr Lydie Cassard

Assistant professor
Dr Marie Naigeon

Engineer
Jean Jouniaux:

Engineer
Lisa Boselli

Technician
Jonathan Grivel:

Main publications

• Loriot Y, Marabelle A, Guégan JP, Danlos FX, Besse B, Chaput N, Massard C, Planchard D, Robert C, Even C, Khettab M, Tselika L, Friboulet L, André F, Nafia I, Le Loarer F, Soria JC, Bessede A, Italiano A. Plasma proteomics identifies Leukemia Inhibitory Factor (LIF) as a novel predictive biomarker of immune-checkpoint blockade resistance. Ann Oncol. 2021 Aug 17:S0923-7534(21)03978-8. doi: 10.1016/j.annonc.2021.08.1748. Epub ahead of print. PMID: 34416362.
• Terry S, Dalban C, Rioux Leclercq N, Adam J, Meylan M, Buart S, Bougoüin A, Lespagnol A, Dugay F, Colina Moreno I, Lacroix G, Lorens JB, Gausdal G, Fridman WH, Mami-Chouaib F, Chaput N, Beuselinck B, Chabaud S, Barros Monteiro J, Vano Y, Escudier B, Sautes-Fridman C, Albiges L, Chouaib S. Association of AXL and PD-L1 expression with clinical outcomes in patients with advanced renal cell carcinoma treated with PD-1 blockade. Clin Cancer Res. 2021 Aug 18:clincanres.0972.2021. doi: 10.1158/1078-0432.CCR-21-0972. Epub ahead of print. PMID: 34407968.
• Pham F, Moinard-Butot F, Coutzac C, Chaput N. Cancer and immunotherapy: a role for microbiota composition. Eur J Cancer. 2021 Sep;155:145-154. doi: 10.1016/j.ejca.2021.06.051. Epub 2021 Aug 7. PMID: 34375896.
• Duchemann B, Remon J, Naigeon M, Cassard L, Jouniaux JM, Boselli L, Grivel J, Auclin E, Desnoyer A, Besse B, Chaput N. Current and future biomarkers for outcomes with immunotherapy in non-small cell lung cancer. Transl Lung Cancer Res. 2021 Jun;10(6):2937-2954. doi: 10.21037/tlcr-20-839. PMID: 34295689; PMCID: PMC8264336.
• Mezquita L, Preeshagul I, Auclin E, Saravia D, Hendriks L, Rizvi H, Park W, Nadal E, Martin-Romano P, Ruffinelli JC, Ponce S, Audigier-Valette C, Carnio S, Blanc-Durand F, Bironzo P, Tabbò F, Reale ML, Novello S, Hellmann MD, Sawan P, Girshman J, Plodkowski AJ, Zalcman G, Majem M, Charrier M, Naigeon M, Rossoni C, Mariniello A, Paz-Ares L, Dingemans AM, Planchard D, Cozic N, Cassard L, Lopes G, Chaput N, Arbour K, Besse B. Predicting immunotherapy outcomes under therapy in patients with advanced NSCLC using dNLR and its early dynamics. Eur J Cancer. 2021 Jul;151:211-220. doi: 10.1016/j.ejca.2021.03.011. Epub 2021 May 19. PMID: 34022698.
• Duchemann B, Remon J, Naigeon M, Mezquita L, Ferrara R, Cassard L, Jouniaux JM, Boselli L, Grivel J, Auclin E, Desnoyer A, Besse B, Chaput N. Integrating Circulating Biomarkers in the Immune Checkpoint Inhibitor Treatment in Lung Cancer. Cancers (Basel). 2020 Dec 3;12(12):3625. doi: 10.3390/cancers12123625. PMID: 33287347; PMCID: PMC7761725.
• Rivière E, Pascaud J, Virone A, Dupré A, Ly B, Paoletti A, Seror R, Tchitchek N, Mingueneau M, Smith N, Duffy D, Cassard L, Chaput N, Pengam S, Gauttier V, Poirier N, Mariette X, Nocturne G. Interleukin-7/Interferon Axis Drives T Cell and Salivary Gland Epithelial Cell Interactions in Sjögren's Syndrome. Arthritis Rheumatol. 2021 Apr;73(4):631-640. doi: 10.1002/art.41558. Epub 2021 Feb 15. PMID: 33058491.
• De Giglio A, Mezquita L, Auclin E, Blanc-Durand F, Riudavets M, Caramella C, Martinez G, Benitez JC, Martín-Romano P, El-Amarti L, Hendriks L, Ferrara R, Naltet C, Lavaud P, Gazzah A, Adam J, Planchard D, Chaput N, Besse B. Impact of Intercurrent Introduction of Steroids on Clinical Outcomes in Advanced Non-Small-Cell Lung Cancer (NSCLC) Patients under Immune-Checkpoint Inhibitors (ICI). Cancers (Basel). 2020 Sep 30;12(10):2827. doi: 10.3390/cancers12102827. PMID: 33007977; PMCID: PMC7599488.
• Ferrara R, Naigeon M, Auclin E, Duchemann B, Cassard L, Jouniaux JM, Boselli L, Grivel J, Desnoyer A, Mezquita L, Texier M, Caramella C, Hendriks L, Planchard D, Remon J, Sangaletti S, Proto C, Garassino MC, Soria JC, Marabelle A, Voisin AL, Farhane S, Besse B, Chaput N. Circulating T-cell Immunosenescence in Patients with Advanced Non-small Cell Lung Cancer Treated with Single-agent PD-1/PD-L1 Inhibitors or Platinum-based Chemotherapy. Clin Cancer Res. 2021 Jan 15;27(2):492-503. doi: 10.1158/1078-0432.CCR-20-1420. Epub 2020 Sep 4. PMID: 32887723.
• Delahousse J, Skarbek C, Desbois M, Perfettini JL, Chaput N, Paci A. Oxazaphosphorines combined with immune checkpoint blockers: dose-dependent tuning between immune and cytotoxic effects. J Immunother Cancer. 2020 Aug;8(2):e000916. doi: 10.1136/jitc-2020-000916. PMID: 32784216; PMCID: PMC7418776.
• Desbois M, Béal C, Charrier M, Besse B, Meurice G, Cagnard N, Jacques Y, Béchard D, Cassard L, Chaput N. IL-15 superagonist RLI has potent immunostimulatory properties on NK cells: implications for antimetastatic treatment. J Immunother Cancer. 2020 Jun;8(1):e000632. doi: 10.1136/jitc-2020-000632. PMID: 32532840; PMCID: PMC7295443.
• Coutzac C, Jouniaux JM, Paci A, Schmidt J, Mallardo D, Seck A, Asvatourian V, Cassard L, Saulnier P, Lacroix L, Woerther PL, Vozy A, Naigeon M, Nebot-Bral L, Desbois M, Simeone E, Mateus C, Boselli L, Grivel J, Soularue E, Lepage P, Carbonnel F, Ascierto PA, Robert C, Chaput N. Systemic short chain fatty acids limit antitumor effect of CTLA-4 blockade in hosts with cancer. Nat Commun. 2020 May 1;11(1):2168. doi: 10.1038/s41467-020-16079-x. PMID: 32358520; PMCID: PMC7195489.
• Michot JM, Albiges L, Chaput N, Saada V, Pommeret F, Griscelli F, Balleyguier C, Besse B, Marabelle A, Netzer F, Merad M, Robert C, Barlesi F, Gachot B, Stoclin A. Tocilizumab, an anti-IL-6 receptor antibody, to treat COVID-19-related respiratory failure: a case report. Ann Oncol. 2020 Jul;31(7):961-964. doi: 10.1016/j.annonc.2020.03.300. Epub 2020 Apr 2. PMID: 32247642; PMCID: PMC7136869.
• Mir O, Broutin S, Desnoyer A, Delahousse J, Chaput N, Paci A. Pharmacokinetics/Pharmacodynamic (PK/PD) relationship of therapeutic monoclonal antibodies used in oncology: what's new? Eur J Cancer. 2020 Mar;128:103-106. doi: 10.1016/j.ejca.2020.01.004. Epub 2020 Feb 20. PMID: 32089494.