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Engineered allogeneic stem cells orchestrate T lymphocyte driven immunotherapy in immunosuppressive leptomeningeal brain metastasis.

J Natl Cancer Inst

January 2025

Center for Stem Cell and Translational Immunotherapy, Brigham and Women's Hospital, Harvard Medical School, Boston, 02115, Massachusetts, USA.

Background: Immune-checkpoint inhibitors have shown clinical benefit in non-small cell lung cancer (NSCLC) derived brain metastasis (BM), however, their efficacy in lung to leptomeningeal brain metastasis (LLBM) remains poor.

Methods: A paired matched RNA expression dataset of patients with NSCLCs and BMs was analyzed to idenfiy BM specific suppressive tumor microenvironment (TME) features. Next, we created immune-competent LLBM mouse models that mimic clinical LLBM.

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IL-35 modulates Tfh2 and Tfr cell balance to alleviate allergic rhinitis.

Inflamm Res

January 2025

Department of Otolaryngology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510623, China.

Background: Allergic rhinitis (AR) represents a persistent inflammatory condition affecting the upper respiratory tract, characterized by abnormal initiation of the immunoglobulin E (IgE)-mediated cascade. Follicular helper T (Tfh) cells and regulatory T (Tfr) cells are pivotal in orchestrating the development of IgE production in AR patients. IL-35, an anti-inflammatory cytokine, secreted by various cellular subpopulations.

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Dimethyl fumarate (DMF) is an anti-inflammatory and immunoregulatory medication used to treat multiple sclerosis (MS) and psoriasis. Its skin sensitization property precludes its topical use, which is unfortunate for the treatment of psoriasis. Isosorbide di-(methyl fumarate) (IDMF), a novel derivative of DMF, was synthesized to circumvent this adverse reaction and unlock the potential of topical delivery, which could be useful for treating psoriasis in the subpopulation of psoriatic MS patients, as well as in the general population.

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Background: Pancreatic ductal adenocarcinoma (PDAC) is mostly refractory to immunotherapy due to immunosuppression in the tumor microenvironment and cancer cell-intrinsic T cell tolerance mechanisms. PDAC is described as a "cold" tumor type with poor infiltration by T cells and factors leading to intratumoral T cell suppression have thus received less attention. Here, we identify a cancer cell-intrinsic mechanism that contributes to a T cell-resistant phenotype and describes potential combinatorial therapy.

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Slamming hepatocellular carcinoma: targeting immunosuppressive macrophages via SLAMF7 reprograms the tumor microenvironment.

Transl Cancer Res

December 2024

Department of Hepatology and Gastroenterology, Campus Charité Mitte and Campus Virchow-Klinikum, Charité-Universitätsmedizin Berlin, Berlin, Germany.

Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer and one of the leading causes of cancer-related deaths worldwide due to limited treatment options. The tumor microenvironment (TME), which is usually immunosuppressive in HCC, appears to be a decisive factor for response to immunotherapy and strategies aimed at inducing a more inflamed TME hold promise to overcome resistance to immunotherapy. Within the TME, the interplay of various cell types determines whether immunotherapy is successful.

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