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

Reversing immunosuppression

Our lab has contributed to elucidating the pro-angiogenic and pro-tumoral functions of macrophages in mouse models of cancer. We have also characterized VEGFA-independent modes of tumor angiogenesis, and illustrated the therapeutic opportunities afforded by inhibiting angiopoietin signaling in de novo models of metastatic cancer. Currently, we employ genetic cancer models and cell-engineering strategies, largely based on lentiviral gene transfer, to dissect the interactions between macrophages, blood vessels and T cells in tumors, primarily by focusing on angiogenic signaling, immune checkpoints, microRNA regulation, and secreted exosomes. By tackling these processes, we aim to reprogram the immunosuppressive tumor microenvironment to a form that enhances the efficacy of anticancer therapies and facilitates the deployment of anti-tumor immunity.

Engineering immune cells

Conventional dendritic cell vaccines have delivered mixed clinical results. We have recently developed a new platform of gene-modified dendritic cells that activate the immune system against cancer. Our proprietary platform consists of a chimeric receptor, termed extracellular vesicle-internalizing receptor (EVIR), which endows dendritic cells with the ability to uptake extracellular vesicles released from the patient’s own tumor and to present EV-associated tumor antigens to the immune system, without knowledge or manipulation of tumor antigens ex vivo. EVIR-engineered dendritic cells represent a new class of tumor vaccine for personalized therapeutic applications. We are committed to clinically test our innovative vaccination strategy and deploy it to patients with cancer.


Lab 2022

Other members

Selected Publications

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

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