Publications by authors named "S P Malu"
Article Synopsis
- - Resistance to immune checkpoint inhibitors (ICIs) in cancer therapy remains a significant obstacle, prompting researchers to develop a new technique called Perturb-CITE-sequencing (Perturb-CITE-seq) to investigate this issue.
- - The study analyzed over 218,000 patient-derived melanoma cells and tumor-infiltrating lymphocyte co-cultures, identifying known and new mechanisms of immune resistance, including defects in specific signaling pathways and the downregulation of a protein called CD58.
- - CD58 loss was linked to immune evasion in melanoma, and interestingly, its expression wasn't affected by interferon-γ signaling, indicating it interacts differently than previously known resistance mechanisms, thus paving the way for better understanding
Aurora kinase inhibition sensitizes melanoma cells to T-cell-mediated cytotoxicity.
Cancer Immunol Immunother
April 2021
Although immunotherapy has achieved impressive durable clinical responses, many cancers respond only temporarily or not at all to immunotherapy. To find novel, targetable mechanisms of resistance to immunotherapy, patient-derived melanoma cell lines were transduced with 576 open reading frames, or exposed to arrayed libraries of 850 bioactive compounds, prior to co-culture with autologous tumor-infiltrating lymphocytes (TILs). The synergy between the targets and TILs to induce apoptosis, and the mechanisms of inhibiting resistance to TILs were interrogated.
View Article and Find Full Text PDFDevelopment of ion pairing LC-MS/MS method for itaconate and cis-aconitate in cell extract and cell media.
J Chromatogr B Analyt Technol Biomed Life Sci
June 2020
Accumulation of Immune Responsive Gene 1(IRG1) in macrophage induced by lipopolysaccharide (LPS) and interferon gamma (IFN-γ) leads to production of itaconate by decarboxylation of cis-aconitate. The biology associated with IRG1 and itaconate is not fully understood. A rapid and sensitive method for measurement of itaconate will benefit the study of IRG1 biology.
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- * The research reveals a resistance program in malignant cells that leads to immune evasion, characterized by T cell exclusion and present before immunotherapy begins; this program can help predict which patients will respond to anti-PD-1 therapy.
- * Combining CDK4/6 inhibitors with immunotherapy shows promise, as it can suppress the resistance program in cancer cells, induce cell senescence, and reduce tumor growth in mouse models, suggesting new treatment strategies for overcoming resistance to ICI.
Adoptive T cell therapy (ACT) produces durable responses in some cancer patients; however, most tumors are refractory to ACT and the molecular mechanisms underlying resistance are unclear. Using two independent approaches, we identified tumor glycolysis as a pathway associated with immune resistance in melanoma. Glycolysis-related genes were upregulated in melanoma and lung cancer patient samples poorly infiltrated by T cells.
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