Immune Responses to Cancer

Sebastian AMIGORENA - credit Thibaut Voisin 1 copie copie

Sebastian Amigorena Team Leader Tel:

Adaptive immune responses are initiated by the clonal selection of naive T lymphocytes, which recognize their cognate ligands through antigen-specific T cell receptors. T cell receptors are specific for MHC/peptides complexes. These peptides are generated from internalized antigens that are degraded in endocytic compartments. The peptides are then loaded on MHC molecules and the complexes are transported to the cell surface. Clonal selection also requires the physical encounter of dendritic cells and T lymphocytes, an event that occurs in the T cell zones of lymph nodes. Naïve T cells then expand and differentiate into effector T lymphocytes that acquire either cytotoxic activity or secrete high amounts of certain cytokines. Some of these T cells become “effectos” (the ones that have direct roles in the immune response, including helper functions for CD4+ T cells, and cytotoxic functions for CD8+ T cells), while other T cells differentiate into resting memory cells. The latter are longed lived and can be reactivated upon re-infection with the same microbe, initiating a more rapide and effective recall response.

Figure 1 : Phagosomal degradation of OVA is dependent on phagosome maturation kinetics. (A) Latex beads conjugated to OVA were internalized by bone marrow-derived dendritic cells (DC) and macrophages (MO) and analyzed by confocal microscopy after labeling of OVA (blue), LAMP-1 (red) and F-actin (green). Shown are maximum projections of 5 focal planes with a step width of 0.3 μm. Bar: 10 μm.
Figure 1 : Phagosomal degradation of OVA is dependent on phagosome maturation kinetics. (A) Latex beads conjugated to OVA were internalized by bone marrow-derived dendritic cells
(DC) and macrophages (MO) and analyzed by confocal microscopy after labeling of OVA (blue), LAMP-1 (red) and F-actin (green). Shown are maximum projections of 5 focal planes with a step width
of 0.3 μm. Bar: 10 μm.

Our team is interested in the molecular analysis of immune responses, particularly in the context of cancer. Our main objectives are:

  • To understand the molecular basis of antigen presentation in dendritic cells. We analyse the intracellular membrane transport pathways involved and attempt to identify the intracellular compartments where peptide-MHC complexes form. We also investigate the ability and involvement of different mouse and human DC population in immune responses against tumors.
  • To analyse the molecular determinants that control gene expression during T cell differentiation and the generation of immunological memory. We attempt to understand how the organisation of chromatin determines the epigenetic control of T cell responses in vitro and in vivo.
Figure 2: Using bone marrow chimeric mice, adoptively transferred tumors expressing different fluorescent proteins and in vivo infusion of propidium iodide, we can follow dynamically anti tumor T cells (here in light blue; false color) dead tumor cells (in red) and collagen fibers (blue, second harmonics).
Figure 2: Using bone marrow chimeric mice, adoptively transferred tumors expressing different fluorescent proteins and in vivo infusion of propidium iodide, we can follow dynamically anti tumor T cells (here in light blue; false color) dead tumor cells (in red) and collagen fibers (blue, second harmonics).

Our technological expertise ranges from the most fundamental approaches to study membrane transport in lymphocytes and dendritic cells (subcellular compartmentalization, intravital microscopy, phagosomal functions), the systematic analysis of gene expression and it regulation (RNAseq, Chip Seq, proteomics) and physiological and pathological immune responses (mouse models for cancer immunity, immunomodulation/vaccination, human clinical studies in cancer).

Key publications

Year of publication 2020

Marianne Burbage, Sebastian Amigorena (2020 Aug 14)

A dendritic cell multitasks to tackle cancer.

Nature : 533-534 : DOI : 10.1038/d41586-020-02339-9
Nicolas Gonzalo Núñez, Jimena Tosello Boari, Rodrigo Nalio Ramos, Wilfrid Richer, Nicolas Cagnard, Cyrill Dimitri Anderfuhren, Leticia Laura Niborski, Jeremy Bigot, Didier Meseure, Philippe De La Rochere, Maud Milder, Sophie Viel, Delphine Loirat, Louis Pérol, Anne Vincent-Salomon, Xavier Sastre-Garau, Becher Burkhard, Christine Sedlik, Olivier Lantz, Sebastian Amigorena, Eliane Piaggio (2020 Jul 1)

Tumor invasion in draining lymph nodes is associated with Treg accumulation in breast cancer patients.

Nature communications : 3272 : DOI : 10.1038/s41467-020-17046-2

Year of publication 2019

Kondratova M1, Czerwinska U1,2, Sompairac N1,2, Amigorena SD3, Soumelis V3, Barillot E1, Zinovyev A1, Kuperstein I4. (2019 Oct 22)

A multiscale signalling network map of innate immune response in cancer reveals cell heterogeneity signatures.

Nature communications : 10 : Nat Commun. 2019 Oct 22;10(1):4808. doi: 10.1038/s41467-019-12270-x. : 4808 : DOI : 10.1038/s41467-019-12270-x

Year of publication 2017

Goudot C1, Coillard A1, Villani AC2, Gueguen P1, Cros A1, Sarkizova S3, Tang-Huau TL4, Bohec M5, Baulande S5, Hacohen N2, Amigorena S1, Segura E6. (2019 Sep 19)

Aryl Hydrocarbon Receptor Controls Monocyte Differentiation into Dendritic Cells versus Macrophages.

Immunity : 47 : Immunity. 2017 Sep 19;47(3):582-596.e6. doi: 10.1016/j.immuni.2017.08.016. : 582,596 : DOI : 10.1016/j.immuni.2017.08.016

Year of publication 2019

Coillard A1,2, Segura E1. (2019 Aug 13)

In vivo Differentiation of Human Monocytes.

Frontiers in immunology : 10 : 1907 : DOI : 10.3389/fimmu.2019.01907

Year of publication 2015

Bonsang-Kitzis H1, Sadacca B2, Hamy-Petit AS3, Moarii M4, Pinheiro A3, Laurent C3, Reyal F1. (2019 Jun 24)

Biological network-driven gene selection identifies a stromal immune module as a key determinant of triple-negative breast carcinoma prognosis.

Oncoimmunology : 5 : 1061176 : DOI : 10.1080/2162402X.2015.1061176
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