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Chimeric antigen receptor macrophages (CAR-M) sensitize HER2+ solid tumors to PD1 blockade in pre-clinical models.
Nat Commun
January 2025
Carisma Therapeutics Inc, Philadelphia, PA, USA.
We previously developed human CAR macrophages (CAR-M) and demonstrated redirection of macrophage anti-tumor function leading to tumor control in immunodeficient xenograft models. Here, we develop clinically relevant fully immunocompetent syngeneic models to evaluate the potential for CAR-M to remodel the tumor microenvironment (TME), induce T cell anti-tumor immunity, and sensitize solid tumors to PD1/PDL1 checkpoint inhibition. In vivo, anti-HER2 CAR-M significantly reduce tumor burden, prolong survival, remodel the TME, increase intratumoral T cell and natural killer (NK) cell infiltration, and induce antigen spreading.
View Article and Find Full Text PDFDeveloping and experimental validating a T cell senescence-related gene signature to predict prognosis and immunotherapeutic sensitivity in non-small cell lung cancer.
Gene
January 2025
Department of Thoracic Oncology Surgery, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou 350011 Fujian Province, PR China. Electronic address:
Background: T cell senescence affects non-small cell lung cancer (NSCLC) by compromising the anti-tumor immune response. However, the prognostic significance of T cell senescence-related genes in NSCLC remains unclear.
Methods: The scRNA-seq data from normal lung and NSCLC tissues, along with co-incubation experiments involving NSCLC cells and T cells, were utilized to identify T cell senescence characteristics.
Flow Cytometric Assessment of FcγRIIIa-V158F Polymorphisms and NK Cell Mediated ADCC Revealed Reduced NK Cell Functionality in Colorectal Cancer Patients.
Cells
December 2024
BIH Center for Regenerative Therapies (BCRT), Therapy-Induced Remodeling in Immuno-Oncology, Berlin Institute of Health at Charité-Universitätsmedizin Berlin, 13353 Berlin, Germany.
Antibody-dependent cell-mediated cytotoxicity (ADCC) by NK cells is a key mechanism in anti-cancer therapies with monoclonal antibodies, including cetuximab (EGFR-targeting) and avelumab (PDL1-targeting). Fc gamma receptor IIIa (FcγRIIIa) polymorphisms impact ADCC, yet their clinical relevance in NK cell functionality remains debated. We developed two complementary flow cytometry assays: one to predict the FcγRIIIa-V158F polymorphism using a machine learning model, and a 15-color flow cytometry panel to assess antibody-induced NK cell functionality and cancer-immune cell interactions.
View Article and Find Full Text PDFImmunogenomic determinants of exceptional response to immune checkpoint inhibition in renal cell carcinoma.
Nat Cancer
January 2025
Department of Hematopoietic Biology and Malignancy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Immune checkpoint inhibitors can lead to 'exceptional', durable responses in a subset of persons. However, the molecular basis of exceptional response (ER) to immunotherapy in metastatic clear cell renal cell carcinoma (mccRCC) has not been well characterized. Here we analyzed pretherapy genomic and transcriptomic data in treatment-naive persons with mccRCC treated with standard-of-care immunotherapies: (1) combination of programmed cell death protein and ligand 1 (PD1/PDL1) and cytotoxic T lymphocyte-associated protein 4 inhibitors (IO/IO) or (2) combination of PD1/PDL1 and vascular endothelial growth factor (VEGF) receptor inhibitors (IO/VEGF).
View Article and Find Full Text PDFAnti-PD1-/PDL1-induced chronic intestinal pseudo-obstruction: three cases treated with vedolizumab after corticosteroid failure with mixed results.
Cancer Immunol Immunother
January 2025
Department of Medical Oncology, Institut de Cancérologie de L'Ouest, 44805, Saint Herblain, France.
Article Synopsis
- Immune checkpoint inhibitors (ICI) have transformed cancer treatment but can lead to rare and serious neurological side effects, such as chronic intestinal pseudo-obstruction (CIPO).
- CIPO may be linked to T cell infiltration and presents with vague symptoms like nausea and constipation, complicating diagnosis and treatment.
- In three cases treated with vedolizumab after corticosteroids failed, there was minimal improvement, suggesting vedolizumab is not an effective option for ICI-induced CIPO at this time.
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