Pauline Hamon
Assistant Professor
(CPJ, France tenure track position)
Overview
Macrophages represent a heterogeneous and abundant cell type in solid cancers. Their complexity arises in their diversity of function, where macs can not only suppress anti-tumor immunity but also play crucial roles in tissue organization, T cell interaction and activation, and tissue repair. Another layer of their complexity comes from their origin, either long-lived, embryonically derived tissue-resident macrophages or monocyte-derived macrophages recruited from the circulation, as well as their different contribution depending on the tumor-tissue of origin.
Therefore, a more nuanced approach that targets specific mac programs while preserving their beneficial functions is required to overcome resistance to immunotherapy and prevent potential relapse.
Research projects
1 – Macrophage diversity during tumor progression and relapse across solid cancers
Patient cohort analysis :
We leverage patient cohorts of hepatocellular carcinoma (HCC) and non-small cell lung cancer (NSCLC) to investigate how macrophage activation states and spatial localization associate with clinical outcomes. We aim to understand how tumor heterogeneity, such as tissue of origin, fibrosis, immune infiltration, and the presence of tertiary lymphoid structures (TLS), shapes macrophage diversity.
Preclinical models to dissect macrophage programs :
We use complementary mouse models to study macrophage dynamics across solid tumors and link specific programs to tumor progression and metastasis. Our focus includes :
- The contribution of tissue-resident macrophages to tumor development and relapse
- Macrophage-stroma interactions during immune exclusion and their role in resistance to therapy
2 – Macrophage targeting to enhance immunotherapy efficacy
Preclinical models to evaluate macrophage-targeted strategies :
We develop and refine preclinical models to dissect the role of macrophage programs in modulating the response to immunotherapy. Our goal is to identify selective macrophage-targeting approaches to enhance therapeutic efficacy.
Ex vivo tissue slice culture platform :
We are establishing a pipeline using fresh tissue slice cultures (TSC) to preserve native tissue architecture and macrophage diversity. This ex vivo platform allows for controlled perturbations to study macrophage responses, T cell activation, and tumor cell killing across various solid tumor types.
Principales publications
MARQO pipeline resolves multiparametric cellular and spatial organization in cancer tissue lesions. Mark Buckup, Igor Figueiredo, Giorgio Ioannou, Sinem Ozbey, Rafael Cabal, Alexandra Tabachnikova, Leanna Troncoso, Jessica Le Berichel, Zhen Zhao, Stephen C Ward, Clotilde Hennequin, Guray Akturk, Steve Hamel, Maria Isabel Fiel, Rachel Brody, Myron Schwartz, Thomas U Marron, Seunghee Kim-Schulze, Edgar Gonzalez-Kozlova, Vladimir Roudko, Pauline Hamon, Miriam Merad, Sacha Gnjatic. Nature Biomedical Engineering. 2025 July. Read
Hematopoietic aging promotes cancer by fueling IL-1⍺-driven emergency myelopoiesis. Park MD, Le Berichel J, Hamon P, Wilk CM, Belabed M, Yatim N, Saffon A, Boumelha J, Falcomatà C, Tepper A, Hegde S, Mattiuz R, Soong BY, LaMarche NM, Rentzeperis F, Troncoso L, Halasz L, Hennequin C, Chin T, Chen EP, Reid AM, Su M, Cahn AR, Koekkoek LL, Venturini N, Wood-Isenberg S, D’souza D, Chen R, Dawson T, Nie K, Chen Z, Kim-Schulze S, Casanova-Acebes M, Swirski FK, Downward J, Vabret N, Brown BD, Marron TU, Merad M. Science. 2024 Oct 25;386(6720):eadn0327. doi: 10.1126/science.adn0327. Read
Intratumoral dendritic cell-CD4+ T helper cell niches enable CD8+ T cell differentiation following PD-1 blockade in hepatocellular carcinoma. Magen A, Hamon P, Fiaschi N, Soong BY, Park MD, Mattiuz R, Humblin E, Troncoso L, D’souza D, Dawson T, Kim J, Hamel S, Buckup M, Chang C, Tabachnikova A, Schwartz H, Malissen N, Lavin Y, Soares- Schanoski A, Giotti B, Hegde S, Ioannou G, Gonzalez-Kozlova E, Hennequin C, Le Berichel J, Zhao Z, Ward SC, Fiel I, Kou B, Dobosz M, Li L, Adler C, Ni M, Wei Y, Wang W, Atwal GS, Kundu K, Cygan KJ, Tsankov AM, Rahman A, Price C, Fernandez N, He J, Gupta NT, Kim-Schulze S, Gnjatic S, Kenigsberg E, Deering RP, Schwartz M, Marron TU, Thurston G, Kamphorst AO, Merad M. Nat Med. 2023 Jun;29(6):1389-1399. doi: 10.1038/s41591-023- 02345-0. Read
🔽 Voir les autres publications
TREM2 macrophages drive NK cell paucity and dysfunction in lung cancer. Park MD, Reyes-Torres I, Le Berichel J, Hamon P, LaMarche NM, Hegde S, Belabed M, Troncoso L, Grout JA, Magen A, Humblin E, Nair A, Molgora M, Hou J, Newman JH, Farkas AM, Leader AM, Dawson T, D’Souza D, Hamel S, Sanchez-Paulete AR, Maier B, Bhardwaj N, Martin JC, Kamphorst AO, Kenigsberg E, Casanova-Acebes M, Horowitz A, Brown BD, De Andrade LF, Colonna M, Marron TU, Merad M. Nat Immunol. 2023 May;24(5):792-801. doi: 10.1038/s41590-023-01475-4. Read
On the Biology and Therapeutic Modulation of Macrophages and Dendritic Cells in Cancer. Park MD, Belabed M, Chen ST, Hamon P, Hegde S, Mattiuz M*, Marron TU, Merad M. Annual Review of Cancer Biology, 2023 Apr; pp. 291-311, 10.1146/annurev-cancerbio-061521-085949. Read
TGFβ receptor inhibition unleashes interferon-β production by tumor-associated macrophages and enhances radiotherapy efficacy. Hamon P, Gerbé De Thoré M, Classe M, Signolle N, Liu W, Bawa O, Meziani L, Clémenson C, Milliat F, Deutsch E, Mondini M. J Immunother Cancer. 2022 Mar;10(3):e003519. doi: 10.1136/jitc-2021-003519. Read
Neoadjuvant cemiplimab for resectable hepatocellular carcinoma: a single-arm, open-label, phase 2 trial. Marron TU, Fiel MI, Hamon P, Fiaschi N, Kim E, Ward SC, Zhao Z, Kim J, Kennedy P, Gunasekaran G, Tabrizian P, Doroshow D, Legg M, Hammad A, Magen A, Kamphorst AO, Shareef M, Gupta NT, Deering R, Wang W, Wang F, Thanigaimani P, Mani J, Troncoso L, Tabachnikova A, Chang C, Akturk G, Buckup M, Hamel S, Ioannou G, Hennequin C, Jamal H, Brown H, Bonaccorso A, Labow D, Sarpel U, Rosenbloom T, Sung MW, Kou B, Li S, Jankovic V, James N, Hamon SC, Cheung HK, Sims JS, Miller E, Bhardwaj N, Thurston G, Lowy I, Gnjatic S, Taouli B, Schwartz ME, Merad M. Lancet Gastroenterol Hepatol. 2022 Mar;7(3):219-229. doi: 10.1016/S2468-1253(21)00385-X. Read
Macrophages of distinct origins contribute to tumor development in the lung. Loyher PL, Hamon P, Laviron M, Meghraoui-Kheddar A, Goncalves E, Deng Z, Torstensson S, Bercovici N, Baudesson de Chanville C, Combadière B, Geissmann F, Savina A, Combadière C, Boissonnas A. J Exp Med. 2018 Oct 1;215(10):2536-2553. doi: 10.1084/jem.20180534. Read
Fundings
