De Palma lab

Our research program leverages new cell engineering technologies and pre-clinical trials in genetically engineered mice for advancing the conceptual understanding of the tumor microenvironment. These research efforts are poised to identify new mechanisms and vulnerabilities in the tumor microenvironment that may be harnessed for improving the efficacy and broadening the applicability of immune therapies. Key approaches focus on reprogramming the immunosuppressive and pro-angiogenic tumor microenvironment, which is pursued in mouse cancer models that are stratified according to clinical parameters and through genetic refinement. Our research program also envisions relaunching the clinical applicability of dendritic cell vaccines through an innovative biotechnological platform. ...

Research projects

Engineering immune cells

Conventional dendritic cell (DC) therapies have delivered mixed clinical results. We have recently developed new platforms of gene-modified DCs designed to activate the immune system against cancer. These platforms use DC progenitors (DCPs) engineered to express cytokine payloads and/or novel chimeric receptors. These modifications enable DCs to capture extracellular vesicles (EVs) released from the patient’s own tumor and present EV-associated tumor antigens to the immune system, without requiring prior knowledge or ex vivo manipulation of tumor antigens. Our engineered DCPs represent a new class of cell therapy products for personalized therapeutic applications, which combine well with other anti-cancer treatments such as chemo-immunotherapy and CAR-T cells. We are committed to clinically testing our DC-based strategies and delivering them to patients with cancer.

Reversing immunosuppression

Our lab has contributed to elucidating the pro-angiogenic and pro-tumoral functions of macrophages in mouse cancer models. We have also characterized VEGFA-independent mechanisms of tumor angiogenesis and demonstrated the therapeutic potential of inhibiting angiopoietin signaling in de novo models of metastatic cancer. Currently, we use mouse models of lung cancer, melanoma, and glioblastoma, together with cell-engineering strategies, to disrupt pro-tumoral networks orchestrated by macrophages and blood vessels, while strengthening anti-tumoral networks driven by dendritic cells and T cells. Through these approaches, we aim to reprogram the immunosuppressive tumor microenvironment into one that enhances the efficacy of anticancer therapies and supports the activation of anti-tumor immunity.

Team

Lab 2022

Other members

Selected Publications

Trajectories of macrophage ontogeny and reprogramming in cancer

Duval F, Lourenco J, Hicham M, (...), Fournier N, Mansouri N, De Palma M

iScience – 2025 May 16

Milestones in tumor vascularization and its therapeutic targeting

De Palma M, Hanahan D

Nature Cancer – 2024 Jun 25

Cytokine-armed dendritic cell progenitors for antigen-agnostic cancer immunotherapy.

Ghasemi A, Martinez-Usatorre A, Li L, (...), Migliorini D, Heikenwalder M, De Palma M

Nature Cancer – 2023 Nov 23

Overcoming microenvironmental resistance to PD-1 blockade in genetically engineered lung cancer models.

Martinez-Usatorre A, Kadioglu E, Boivin G, (...), Ries CH, Meylan E, De Palma M

Science translational medicine – 2021 Aug 11

Disentangling the complexity of tumor-derived extracellular vesicles.

Beltraminelli T, Perez CR, De Palma M

Cell reports – 2021 Apr 6

Engineering dendritic cell vaccines to improve cancer immunotherapy.

Perez CR, De Palma M

Nature communications – 2019 Nov 27

Molecular Profiling and Functional Analysis of Macrophage-Derived Tumor Extracellular Vesicles.

Cianciaruso C, Beltraminelli T, Duval F, (...), Ries CH, Ivanisevic J, De Palma M

Cell reports – 2019 Jun 4

Chemotherapy elicits pro-metastatic extracellular vesicles in breast cancer models.

Keklikoglou I, Cianciaruso C, Güç E, (...), Jain RK, Pollard JW, De Palma M

Nature cell biology – 2018 Dec 31

T cell-induced CSF1 promotes melanoma resistance to PD1 blockade.

Neubert NJ, Schmittnaegel M, Bordry N, (...), Foukas PG, De Palma M, Speiser DE

Science translational medicine – 2018 Apr 11

Periostin Limits Tumor Response to VEGFA Inhibition.

Keklikoglou I, Kadioglu E, Bissinger S, (...), Orend G, Ries CH, De Palma M

Cell reports – 2018 Mar 6

EVIR: chimeric receptors that enhance dendritic cell cross-dressing with tumor antigens.

Squadrito ML, Cianciaruso C, Hansen SK, De Palma M

Nature methods – 2018 Jan 22

Microenvironmental regulation of tumour angiogenesis.

De Palma M, Biziato D, Petrova TV

Nature reviews. Cancer – 2017 Jul 14

Dual angiopoietin-2 and VEGFA inhibition elicits antitumor immunity that is enhanced by PD-1 checkpoint blockade.

Schmittnaegel M, Rigamonti N, Kadioglu E, (...), Ooi CH, Laoui D, De Palma M

Science translational medicine – 2017 Apr 12

Suppression of microRNA activity amplifies IFN-γ-induced macrophage activation and promotes anti-tumour immunity.

Baer C, Squadrito ML, Laoui D, (...), Ries CH, Ooi CH, De Palma M

Nature cell biology – 2016 Jun 13

Endogenous RNAs modulate microRNA sorting to exosomes and transfer to acceptor cells.

Squadrito ML, Baer C, Burdet F, (...), Lyle R, Ibberson M, De Palma M

Cell reports – 2014 Aug 21

Role of angiopoietin-2 in adaptive tumor resistance to VEGF signaling blockade.

Rigamonti N, Kadioglu E, Keklikoglou I, (...), Wyser Rmili C, Leow CC, De Palma M

Cell reports – 2014 Jul 31

Macrophage regulation of tumor responses to anticancer therapies.

De Palma M, Lewis CE

Cancer cell – 2013 Mar 18

Targeting the ANG2/TIE2 axis inhibits tumor growth and metastasis by impairing angiogenesis and disabling rebounds of proangiogenic myeloid cells.

Mazzieri R, Pucci F, Moi D, (...), Brown JL, Naldini L, De Palma M

Cancer cell – 2011 Apr 12

Related news

Events

ISREC-SCCL Symposium 2025 | September 1–4

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🌱 Second AGORA Sustainability Day | May 21st

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AGORA PRS Seminar | March 4th

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LabLinks: Tumor immunology and immunotherapy | November 11&12th

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13th Faculty & Staff Annual Retreat, Swiss Cancer Center Leman | September 26 & 27

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PhD Thesis Defense | July 19th

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AGORA PRS | November 7th

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AGORA PRS | October 31st

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Lola and John Grace Distinguished Lecture in Cancer Research, Prof. Egeblad | October 19th, 11.45am

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Lola and John Grace Distinguished Lecture in Cancer Research, Prof. Jolanda de Vries | September 21st

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ISREC-SCCL Symposium 2023 | August 21-24

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AGORA PRS | December 6th

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AGORA PRS | November 29th

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AGORA PRS | November 22nd

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AGORA PRS | October 25th