Martina Molgora, PhD

My main interest is the orchestration of the innate immune response in tumors, with a focus on myeloid cells as key players in immune evasion. I aim to investigate the role of innate immune cells in both resistance and response to therapy, elucidating their intricate interactions within the tumor microenvironment. My ultimate goal is to identify novel therapeutic targets and strategies to enhance treatment efficacy.

Associations

• Immunology
• Gastrointestinal Oncology
• Immuno-Oncology Program

Identity and function of TREM2 macrophages in tumors: During my postdoctoral research, I identified TREM2 as a marker of immunosuppressive macrophages in tumors. I found that TREM2 blockade promotes tumor control and response to therapy and is associated with a beneficial immune response. I now aim at understanding the mechanism and pathways by which TREM2 macrophages develop and accumulate in tumors, with the goal to identify strategies to prevent their expansion and therefore favor the anti-tumor immune response. Impact of soluble TREM2 in cancer: TREM2 is a transmembrane receptor highly expressed in tumor-associated macrophages. TREM2 can be cleaved and released as a soluble form, named soluble TREM2. The impact of soluble TREM2 in cancer is currently unknown. I aim at understanding the potential role of soluble TREM2 as a diagnostic, prognostic and therapeutic factor in different tumor types. I also aim at exploring the mechanisms by which soluble TREM2 might influence the tumor microenvironment. Influence of gut-trafficking cells on systemic immunity and distant-site tumors: Numerous studies have reported the impact of the gut environment on different conditions, although the underlying molecular mechanism still needs to be fully elucidated and multiple questions remain open regarding the interaction between the gut and immune responses at distant sites. Gut-resident cells can sense local signals from both microbes and other cells and represent a potential intermediary element between the gut and distant site organs. My goal is to explore the impact of gut-trafficking cells in tumors and in different physiological and pathological scenarios.

• Molgora M, Colonna M. Targeting brain macrophages: NF-κB as a therapeutic gateway in melanoma brain metastasis. Cancer Cell. 2025 Mar.43(3):328-329. Pubmedid: 40068588.
• Biniaris-Georgallis SI, Aschman T, Stergioula K, Schreiber F, Jafari V, Taranko A, Karmalkar T, Kasapi A, Lenac Rovis T, Jelencic V, Bejarano DA, Fabry L, Papacharalampous M, Mattiola I, Molgora M, Hou J, Hublitz KW, Heinrich F, Guerra GM, Durek P, Patone G, Lindberg EL, Maatz H, Hölsken O, Krönke G, Mortha A, Voll RE, Clarke AJ, Hauser AE, Colonna M, Thurley K, Schlitzer A, Schneider C, Stamatiades EG, Mashreghi MF, Jonjic S, Hübner N, Diefenbach A, Kanda M, Triantafyllopoulou A. Amplification of autoimmune organ damage by NKp46-activated ILC1s. Nature. 2024 Oct.634(8035):952-960. Pubmedid: 39137897.
• Keshari S, Shavkunov AS, Miao Q, Saha A, Minowa T, Molgora M, Williams CD, Chaib M, Highsmith AM, Pineda JE, Alekseev S, Alspach E, Hu KH, Colonna M, Pauken KE, Chen K, Gubin MM. Comparing neoantigen cancer vaccines and immune checkpoint therapy unveils an effective vaccine and anti-TREM2 macrophage-targeting dual therapy. Cell Rep. 2024 Nov.43(11):114875. Pubmedid: 39446585.
• Di Luccia B, Molgora M, Khantakova D, Jaeger N, Chang HW, Czepielewski RS, Helmink BA, Onufer EJ, Fachi JL, Bhattarai B, Trsan T, Rodrigues PF, Hou J, Bando JK, da Silva CS, Cella M, Gilfillan S, Schreiber RD, Gordon JI, Colonna M. TREM2 deficiency reprograms intestinal macrophages and microbiota to enhance anti-PD-1 tumor immunotherapy. Sci Immunol. 2024 May.9(95):eadi5374. Pubmedid: 38758808. Pmcid: PMC11299520.
• Peng V, Trsan T, Sudan R, Bhattarai B, Cortez VS, Molgora M, Vacher J, Colonna M. Inositol phosphatase INPP4B sustains ILC1s and intratumoral NK cells through an AKT-driven pathway. J Exp Med. 2024 Mar.221(3). Pubmedid: 38197946. Pmcid: PMC10783437.
• Timperi E, Croizer H, Khantakova D, Rana M, Molgora M, Guerriero JL, Mechta-Grigoriou F, Romano E. At the Interface of Tumor-Associated Macrophages and Fibroblasts: Immune-Suppressive Networks and Emerging Exploitable Targets. Clin Cancer Res. 2024 Dec.30(23):5242-5251. Pubmedid: 39311702.
• Park MD, Reyes-Torres I, LeBerichel 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. TREM2 macrophages drive NK cell paucity and dysfunction in lung cancer. Nat Immunol. 2023 May.24(5):792-801. Pubmedid: 37081148. Pmcid: PMC11088947.
• Molgora M, Liu YA, Colonna M, Cella M. TREM2: A new player in the tumor microenvironment. Semin Immunol. 2023 May.67:101739. Pubmedid: 36989543.
• Brioschi S, Belk JA, Peng V, Molgora M, Rodrigues PF, Nguyen KM, Wang S, Du S, Wang WL, Grajales-Reyes GE, Ponce JM, Yuede CM, Li Q, Baer JM, DeNardo DG, Gilfillan S, Cella M, Satpathy AT, Colonna M. A Cre-deleter specific for embryo-derived brain macrophages reveals distinct features of microglia and border macrophages. Immunity. 2023 May.56(5):1027-1045.e8. Pubmedid: 36791722. Pmcid: PMC10175109.
• Timperi E, Gueguen P, Molgora M, Magagna I, Kieffer Y, Lopez-Lastra S, Sirven P, Baudrin LG, Baulande S, Nicolas A, Champenois G, Meseure D, Vincent-Salomon A, Tardivon A, Laas E, Soumelis V, Colonna M, Mechta-Grigoriou F, Amigorena S, Romano E. Lipid-Associated Macrophages Are Induced by Cancer-Associated Fibroblasts and Mediate Immune Suppression in Breast Cancer. Cancer Res. 2022 Sep.82(18):3291-3306. Pubmedid: 35862581.
• Nour J, Moregola A, Molgora M, Mantovani A, Uboldi P, Catapano AL, Garlanda C, Bonacina F, Norata GD. Interleukin 1 Receptor 8 Deficiency Does not Impact Atherosclerosis. Thromb Haemostasis. 2022 Oct.122(10):1833-1836. Pubmedid: 35436796.
• Khantakova D, Brioschi S, Molgora M. Exploring the Impact of TREM2 in Tumor-Associated Macrophages. Vaccines (Basel). 2022 Jun.10(6). Pubmedid: 35746551. Pmcid: PMC9227554.
• Molgora M, Colonna M. Innate-like T cells: A promising asset in anti-cancer immunity. Cancer Cell. 2022 Jul.40(7):714-716. Pubmedid: 35714605. Pmcid: PMC9359000.
• Paavola KJ, Roda JM, Lin VY, Chen P, O'Hollaren KP, Ventura R, Crawley SC, Li B, Chen HH, Malmersjö S, Sharkov NA, Horner G, Guo W, Kutach AK, Mondal K, Zhang Z, Lichtman JS, Song C, Rivera LB, Liu W, Luo J, Wang Y, Solloway MJ, Allan BB, Kekatpure A, Starck SR, Haldankar R, Fan B, Chu C, Tang J, Molgora M, Colonna M, Kaplan DD, Hsu JY. The Fibronectin-ILT3 Interaction Functions as a Stromal Checkpoint that Suppresses Myeloid Cells. Cancer Immunol Res. 2021 Nov.9(11):1283-1297. Pubmedid: 34426457. Pmcid: PMC9414285.
• Molgora M, Colonna M. Turning enemies into allies-reprogramming tumor-associated macrophages for cancer therapy. Med (N Y). 2021 Jun.2(6):666-681. Pubmedid: 34189494. Pmcid: PMC8238417.
• Molgora M, Cortez VS, Colonna M. Killing the Invaders: NK Cell Impact in Tumors and Anti-Tumor Therapy. Cancers (Basel). 2021 Feb.13(4). Pubmedid: 33546248. Pmcid: PMC7913353.
• Molgora M, Esaulova E, Vermi W, Hou J, Chen Y, Luo J, Brioschi S, Bugatti M, Omodei AS, Ricci B, Fronick C, Panda SK, Takeuchi Y, Gubin MM, Faccio R, Cella M, Gilfillan S, Unanue ER, Artyomov MN, Schreiber RD, Colonna M. TREM2 Modulation Remodels the Tumor Myeloid Landscape Enhancing Anti-PD-1 Immunotherapy. Cell. 2020 Aug.182(4):886-900.e17. Pubmedid: 32783918. Pmcid: PMC7485282.
• Bonacina F, Moregola A, Porte R, Baragetti A, Bonavita E, Salatin A, Grigore L, Pellegatta F, Molgora M, Sironi M, Barbati E, Mantovani A, Bottazzi B, Catapano AL, Garlanda C, Norata GD. Pentraxin 3 deficiency protects from the metabolic inflammation associated to diet-induced obesity. Cardiovasc Res. 2019 Nov.115(13):1861-1872. Pubmedid: 30859179.
• Ponzetta A, Carriero R, Carnevale S, Barbagallo M, Molgora M, Perucchini C, Magrini E, Gianni F, Kunderfranco P, Polentarutti N, Pasqualini F, Di Marco S, Supino D, Peano C, Cananzi F, Colombo P, Pilotti S, Alomar SY, Bonavita E, Galdiero MR, Garlanda C, Mantovani A, Jaillon S. Neutrophils Driving Unconventional T Cells Mediate Resistance against Murine Sarcomas and Selected Human Tumors. Cell. 2019 Jul.178(2):346-360.e24. Pubmedid: 31257026. Pmcid: PMC6630709.
• Martini E, Kunderfranco P, Peano C, Carullo P, Cremonesi M, Schorn T, Carriero R, Termanini A, Colombo FS, Jachetti E, Panico C, Faggian G, Fumero A, Torracca L, Molgora M, Cibella J, Pagiatakis C, Brummelman J, Alvisi G, Mazza EMC, Colombo MP, Lugli E, Condorelli G, Kallikourdis M. Single-Cell Sequencing of Mouse Heart Immune Infiltrate in Pressure Overload-Driven Heart Failure Reveals Extent of Immune Activation. Circulation. 2019 Dec.140(25):2089-2107. Pubmedid: 31661975.
• Mattiola I, Tomay F, De Pizzol M, Silva-Gomes R, Savino B, Gulic T, Doni A, Lonardi S, Astrid Boutet M, Nerviani A, Carriero R, Molgora M, Stravalaci M, Morone D, Shalova IN, Lee Y, Biswas SK, Mantovani G, Sironi M, Pitzalis C, Vermi W, Bottazzi B, Mantovani A, Locati M. The macrophage tetraspan MS4A4A enhances dectin-1-dependent NK cell-mediated resistance to metastasis. Nat Immunol. 2019 Aug.20(8):1012-1022. Pubmedid: 31263276. Pmcid: PMC7176488.
• Mantovani A, Dinarello CA, Molgora M, Garlanda C. Interleukin-1 and Related Cytokines in the Regulation of Inflammation and Immunity. Immunity. 2019 Apr.50(4):778-795. Pubmedid: 30995499. Pmcid: PMC7174020.
• Molgora M, Supino D, Mavilio D, Santoni A, Moretta L, Mantovani A, Garlanda C. The yin-yang of the interaction between myelomonocytic cells and NK cells. Scand J Immunol. 2018 Sep.88(3):e12705. Pubmedid: 30048003. Pmcid: PMC6485394.
• Molgora M, Supino D, Mantovani A, Garlanda C. Tuning inflammation and immunity by the negative regulators IL-1R2 and IL-1R8. Immunol Rev. 2018 Jan.281(1):233-247. Pubmedid: 29247989. Pmcid: PMC5922415.
• Molgora M, Bonavita E, Ponzetta A, Riva F, Barbagallo M, Jaillon S, Popović B, Bernardini G, Magrini E, Gianni F, Zelenay S, Jonjić S, Santoni A, Garlanda C, Mantovani A. IL-1R8 is a checkpoint in NK cells regulating anti-tumour and anti-viral activity. Nature. 2017 Nov.551(7678):110-114. Pubmedid: 29072292. Pmcid: PMC5768243.
• Campesato LF, Silva APM, Cordeiro L, Correa BR, Navarro FCP, Zanin RF, Marçola M, Inoue LT, Duarte ML, Molgora M, Pasqualini F, Massara M, Galante P, Barroso-Sousa R, Polentarutti N, Riva F, Costa ET, Mantovani A, Garlanda C, Camargo AA. High IL-1R8 expression in breast tumors promotes tumor growth and contributes to impaired antitumor immunity. Oncotarget. 2017 Jul.8(30):49470-49483. Pubmedid: 28533483. Pmcid: PMC5564782.
• Molgora M, Barajon I, Mantovani A, Garlanda C. Regulatory Role of IL-1R8 in Immunity and Disease. Front Immunol. 2016 Apr.7:149. Pubmedid: 27148268. Pmcid: PMC4837151.
• Mattiola I, Pesant M, Tentorio PF, Molgora M, Marcenaro E, Lugli E, Locati M, Mavilio D. Priming of Human Resting NK Cells by Autologous M1 Macrophages via the Engagement of IL-1β, IFN-β, and IL-15 Pathways. J Immunol. 2015 Sep.195(6):2818-2828. Pubmedid: 26276870.
• Bonavita E, Gentile S, Rubino M, Maina V, Papait R, Kunderfranco P, Greco C, Feruglio F, Molgora M, Laface I, Tartari S, Doni A, Pasqualini F, Barbati E, Basso G, Galdiero MR, Nebuloni M, Roncalli M, Colombo P, Laghi L, Lambris JD, Jaillon S, Garlanda C, Mantovani A. PTX3 is an extrinsic oncosuppressor regulating complement-dependent inflammation in cancer. Cell. 2015 Feb.160(4):700-714. Pubmedid: 25679762.

• Title: IMPACT OF TREM2 ON GASTRIC CANCER
  Award Number: AGA2023-13-06
  Sponsor: American Gastroenterological Association (AGA)
  Molgora, M. (PD/PI)