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Les cellules stromales mésenchymateuses (CSMs) sont généralement connues pour leurs capacités immunosuppressives. Cependant, notre groupe a démontré qu’il est possible de convertir les CSMs en puissantes cellules présentatrices d’antigènes (CPA) en utilisant des techniqeus de génie génétique ou des moyens pharmacologiques. Ce dernier example est particulièrement intéressant compte tenu de la capacité de la molécule UM171a à déclencher une fonction de type CPA dans les CSMs, et de la récente découverte que cette molécule peut moduler l’épigénome en inhibant la déméthylase 1 spécifique de la lysine (LSD1), nous avons exploré si l’inhibition pharmacologique directe du LSD1 pouvait instiller des fonctions de CPA dans les CSMs comme observé avec l’utilisation de l’UM171a. Le traitement des CSMs avec la tranylcypromine (TC), un inhibiteur du LSD1, provoque une réponse au stress de l’ARN double brin (db) ainsi qu’à des éléments réactifs associés, y compris les récepteurs de reconnaissance de formes (PRR), l’interféron de type I (IFN) et les gènes stimulés par l’IFN (ISG). Le résultat net aboutit à une expression améliorée du H2-Kb, et à une stabilité accrue des complexes peptide:MHCI à la surface de la cellule. En conséquence, les CSMs traités au TC stimulent efficacement l’activation des lymphocytes T CD8 et provoquent de puissantes réponses anti-tumorales contre le lymphome T EG.7 dans le contexte de la vaccination prophylactique. Dans l’ensemble, nos résultats révèlent un nouveau protocole pharmacologique dans lequel le ciblage du LSD1 dans les CSMs suscite des capacités de type CPA qui pourraient être facilement exploitées dans la conception de futurs vaccins anti-cancéreux à base de CSMs., Mesenchymal stromal cells (MSCs) are commonly known for their immune-suppressive abilities. However, our group provided evidence that it is possible to convert MSCs into potent antigen presenting cells (APCs) using either genetic engineering or pharmacological means. The latter example is particularly interesting given the capacity of UM171a to trigger APC-like function in MSCs and the recent finding that this drug may modulate the epigenome by inhibiting the lysine-specific demethylase 1 (LSD1). We therefore explored whether direct pharmacological inhibition of LSD1 could instill APC-like functions in MSCs akin to UM171a. Treatment of MSCs with the LSD1 inhibitor tranylcypromine (TC) elicits a double-stranded (ds)RNA stress response along with its associated responsive elements including pattern recognition receptors (PRRs), Type-I interferon (IFN) and IFN-stimulated genes (ISGs). The net outcome culminates in enhanced expression of H2-Kb, and increased stability of the cell surface peptide:MHCI complexes. As a result, TC-treated MSCs stimulate CD8 T-cell activation efficiently and elicit potent anti-tumoral responses against the EG.7 T-cell lymphoma in the context of prophylactic vaccination. Altogether, our findings reveal a new pharmacological protocol whereby targeting LSD1 in MSCs elicits APC-like capabilities that could be easily exploited in the design of future MSC-based anti-cancer vaccines.

The clinical impact of tumor-infiltrating lymphocytes (TILs) is less known for breast cancer patients with the estrogen receptor-positive (ER+)/human epidermal growth factor receptor-negative (HER−) subtype. Here, we explored the prognostic and predictive value of TILs regarding distant recurrence-free interval (DRFI) and breast cancer-specific survival (BCSS) in 763 postmenopausal patients randomized to receive tamoxifen vs. no systemic treatment. TILs were assessed in whole section tumor samples stained with H&E and divided into low (

Soft tissue sarcoma is a heterogeneous disease and treatment options are limited in advanced stage settings. Brivudine is a thymidine-nucleoside analog and inhibits DNA polymerase in VZV infection. We demonstrated a case of a patient who was diagnosed with both VZV infection and advanced stage sarcoma, and unexpected anti-tumoral response after brivudine therapy.

The clinical impact of tumor-infiltrating lymphocytes (TILs) is less known for breast cancer patients with the estrogen receptor-positive (ER+)/human epidermal growth factor receptor-negative (HER−) subtype. Here, we explored the prognostic and predictive value of TILs regarding distant recurrence-free interval (DRFI) and breast cancer-specific survival (BCSS) in 763 postmenopausal patients randomized to receive tamoxifen vs. no systemic treatment. TILs were assessed in whole section tumor samples stained with H&E and divided into low (Funding Agencies|Swedish Research Council (Vetenskapsradet) [2020-02466]; Swedish Research Council for Health, Working life and Welfare, (FORTE) [2019-00477]; Gosta Milton Donation Fund (Stiftelsen Gosta Miltons donationsfond); Swedish Cancer Society (Cancerfonden) [190140, 220552SIA]; Stockholm Cancer Society (Cancerforeningen i Stockholm) [201212]; Svenska Lakarecellskapet

Mesenchymal stromal cells (MSCs) are commonly known for their immune-suppressive abilities. However, our group provided evidence that it is possible to convert MSCs into potent antigen presenting cells (APCs) using either genetic engineering or pharmacological means. Given the capacity of UM171a to trigger APC-like function in MSCs, and the recent finding that this drug may modulate the epigenome by inhibiting the lysine-specific demethylase 1 (LSD1), we explored whether the direct pharmacological inhibition of LSD1 could instill APC-like functions in MSCs akin to UM171a. The treatment of MSCs with the LSD1 inhibitor tranylcypromine (TC) elicits a double-stranded (ds)RNA stress response along with its associated responsive elements, including pattern recognition receptors (PRRs), Type-I interferon (IFN), and IFN-stimulated genes (ISGs). The net outcome culminates in the enhanced expression of H2-Kb, and an increased stability of the cell surface peptide: MHCI complexes. As a result, TC-treated MSCs stimulate CD8 T-cell activation efficiently, and elicit potent anti-tumoral responses against the EG.7 T-cell lymphoma in the context of prophylactic vaccination. Altogether, our findings reveal a new pharmacological protocol whereby targeting LSD1 in MSCs elicits APC-like capabilities that could be easily exploited in the design of future MSC-based anti-cancer vaccines.

Vγ9Vδ2 T cells are important effector cells that may play a role in the anti-tumor immune response. Their capability to exert MHC-nonrestricted lytic activity against different tumor cells in vitro and their detection among tumor infiltrating lymphocytes in a variety of human cancers have supported the development of Vγ9Vδ2 T cell-based immunotherapy in the context of novel treatment against cancer. Accordingly, promising reports from recent clinical trials support the use of V γ9Vδ2 T cells as immunotherapeutic agents, either via adoptive transfer of ex-vivo expanded V γ9Vδ2 T cells or in vivo activation of V γ9Vδ2 T cells with compounds such as phosphoantigens or aminobisphosphonates. In this study we have performed a meta-analysis to assess the objective efficacy and safety of V γ9Vδ2 T cell-based immunotherapy. Database including Pubmed, Web of Science and SCOPUS were investigated to identify relevant studies. Thirteen clinical trials involving patients with advanced or metastatic cancer were selected. In order to estimate the strength of association between V γ9Vδ2 T cell-based immunotherapy and favorable clinical effect or toxicity grade we used event rate (ER) with 95 percent confidence interval (CI). The total effective rate provided significant results (ER = 0.407; P