ChemR23 activation reprograms macrophages toward a less inflammatory phenotype and dampens carcinoma progression.

Introduction: Tumor Associated Macrophages (TAM) are a major component of the tumor environment and their accumulation often correlates with poor prognosis by contributing to local inflammation, inhibition of anti-tumor immune response and resistance to anticancer treatments. In this study, we thus investigated the anti-cancer therapeutic interest to target ChemR23, a receptor of the resolution of inflammation expressed by macrophages, using an agonist monoclonal antibody, αChemR23.

Methods: Human GM-CSF, M-CSF and Tumor Associated Macrophage (TAM)-like macrophages were obtained by incubation of monocytes from healthy donors with GM-CSF, M-CSF or tumor cell supernatants (Breast cancer (BC) or malignant pleural mesothelioma (MPM) cells).

First-in-Human Study in Healthy Subjects with the Noncytotoxic Monoclonal Antibody OSE-127, a Strict Antagonist of IL-7Rα.

OSE-127 is a humanized mAb targeting the IL-7Rα-chain (CD127), under development for inflammatory and autoimmune disease treatment. It is a strict antagonist of the IL-7R pathway, is not internalized by target cells, and is noncytotoxic. In this work, a first-in-human, phase I, randomized, double-blind, placebo-controlled, single-center study was carried out to determine the safety, pharmacokinetics, pharmacodynamics, and immunogenicity of OSE-127 administration.

CLEC-1 is a death sensor that limits antigen cross-presentation by dendritic cells and represents a target for cancer immunotherapy.

Tumors exploit numerous immune checkpoints, including those deployed by myeloid cells to curtail antitumor immunity. Here, we show that the C-type lectin receptor CLEC-1 expressed by myeloid cells senses dead cells killed by programmed necrosis. Moreover, we identified Tripartite Motif Containing 21 (TRIM21) as an endogenous ligand overexpressed in various cancers.

Tumor-associated high endothelial venules mediate lymphocyte entry into tumors and predict response to PD-1 plus CTLA-4 combination immunotherapy.

Recruitment of lymphocytes into tumors is critical for anti-tumor immunity and efficacious immunotherapy. We show in murine models that tumor-associated high endothelial venules (TA-HEVs) are major sites of lymphocyte entry into tumors at baseline and upon treatment with anti-PD-1/anti-CTLA-4 immune checkpoint blockade (ICB). TA-HEV endothelial cells (TA-HECs) derive from post-capillary venules, co-express MECA-79 HEV sialomucins and E/P-selectins, and are associated with homing and infiltration into tumors of various T cell subsets.