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Poster Presentations
P09 Young researchers session
P09.07 Deciphering the nature of the cooperation between monocytes/macrophages and CD8+ T cells during immunotherapy-induced tumor regression
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  1. A Vermare1,2,
  2. A Rouault1,2,
  3. A Ventura3,
  4. B Saint-Pierre1,
  5. W Zeitouni4,
  6. K Mulder5,6,7,
  7. K Bailly1,
  8. B Izac1,
  9. MV Guérin8,
  10. CA Dutertre5,6,9,10 and
  11. N Bercovici1,2
  1. 1Université Paris Cité, Institut Cochin, INSERM, CNRS, Paris, France
  2. 2Equipe Labellisée Ligue Nationale Contre le Cancer (LNCC), Paris, France
  3. 3University of Padova, Padova, Italy
  4. 4GenoSplice Technology, Paris, France
  5. 5Gustave Roussy Cancer Campus, Villejuif, France
  6. 6Institut National de la Santé Et de la Recherche Médicale (INSERM) U1015, Equipe Labellisée-Ligue Nationale contre le Cancer, Villejuif, France
  7. 7Singapore Immunology Network (SIgN), A(∗)STAR, 8A Biomedical Grove, Immunos Building, Singapore, France
  8. 8Institut Pasteur, INSERM U1223, Paris, France
  9. 9Singapore Immunology Network (SIgN), A(∗)STAR, 8A Biomedical Grove, Immunos Building, Singapore, Singapore
  10. 10Translational Immunology Institute, SingHealth/Duke-NUS Academic Medical Centre, the Academia, Singapore, Singapore

Abstract

Background The success of immunotherapy is associated with a remodeling of the entire tumor microenvironment. In this context, a positive cooperation between CD8+ T cells and the activated tumor-infiltrating macrophages and monocytes appear necessary for an optimal tumor regression.However, as the mechanisms of such interactions are still unknown, we aimed to uncover the precise identity of the cooperating monocytes/macrophages and CD8+ T cells as well as the nature of their interplay.

Model In the transplanted PyMT mammary tumor model, we sorted monocytes/macrophages and CD8+ T cells from tumors regressing after STING agonist therapy to perform scRNAseq on these two populations.

Results We discovered that the monocyte/macrophage compartment is divided in three main macrophages subsets and two monocyte-like subsets and that the CD8+ T cells comprise a large diversity of phenotypes (effector, naïve, memory-like, regulatory cells). We have followed the dynamic changes of these populations across the stages of tumor regression and noticed that monocyte-like subsets are preferentially enriched upon regression. In parallel, the CD8+ memory subsets were increased during the regression at the expense of regulatory-like populations.

Perspectives We are currently examining the predicted functions of the different subsets as well as their spatial distribution in the tumor microenvironment, to uncover the mechanisms by which these cells cooperate in tumors treated by immunotherapy.

Disclosure Information A. Vermare: None. A. Rouault: None. A. Ventura: None. B. Saint-Pierre: None. W. Zeitouni: None. K. Mulder: None. K. Bailly: None. B. Izac: None. M.V. Guérin: None. C.A. Dutertre: None. N. Bercovici: None.

http://dx.doi.org/10.1136/jitc-2022-ITOC9.63

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