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Background: T helper (Th) cell subsets primarily assist B cells in differentiating into plasma cells in the germinal center. The mechanism of malignant transformation of plasma cells is an important target for the clinical treatment of MM; however, the mechanism remains unclear.
Methods: We collected the peripheral blood (PB) and bone marrow (BM) samples of 33 patients with MM. In addition, the PB was also collected from 25 normal healthy controls (HCs). We analyzed the percentages of Th cell subsets in the PB and BM samples of patients with MM.
Results: Tfh/CD4 were positively correlated with the proportion of myeloma cells in the BM and PB samples (r = 0.592, P = 0.002 and r = 0.510, P = 0.010 respectively), and showed a strong correlation between the BM and PB samples (r = 0.6559, P = 0.0095). In the PB samples, the percentages of Th2/CD4 and Tfh2/Tfh cells were significantly lower in patients with MM than in HCs (P = 0.00013 and P = 0.0004, respectively), whereas the percentage of Th17/CD4 and Tfh17/Tfh was significantly higher in newly diagnosed patients with MM than in HCs (P = 0.0037 and P = 0.03, respectively), and all these cells showed a good predictive value for MM (area under the curve [AUC] 0.781, = 0.792, = 0.837, and 0.723 respectively). In the PB samples, all subsets of PD-1ICOS Tfh showed a noticeable downward trend in MM from newly diagnosed to non-remission and remission groups. In contrast, all subsets of PD-1ICOS Tfh increased gradually.
Conclusion: Th cell subsets play an important role in the occurrence and development of MM and may provide a fundamental basis for identifying new immunotherapy targets and prognosis.
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http://dx.doi.org/10.3389/fimmu.2024.1445530 | DOI Listing |
Sci Adv
September 2025
Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
(phosphatidylserine synthase 1) encodes an enzyme that facilitates production of phosphatidylserine (PS), which mediates a global immunosuppressive signal. Here, based on in vivo CRISPR screen, we identified PTDSS1 as a target to improve anti-PD-1 therapy. Depletion of in tumor cells increased expression of interferon-γ (IFN-γ)-regulated genes, including , , , and , even in the absence of IFN-γ stimulation in vitro.
View Article and Find Full Text PDFSci Transl Med
September 2025
Key Laboratory of Breast Cancer in Shanghai, Department of Breast Surgery, Precision Cancer Medicine Center, Fudan University Shanghai Cancer Center, Shanghai 200032, P. R. China.
Triple-negative breast cancers (TNBCs) lack predictive biomarkers to guide immunotherapy, especially during early-stage disease. To address this issue, we used single-cell RNA sequencing, bulk transcriptomics, and pathology assays on samples from 171 patients with early-stage TNBC receiving chemotherapy with or without immunotherapy. Our investigation identified an enriched subset of interferon (IFN)-induced CD8 T cells in early TNBC samples, which predict immunotherapy nonresponsiveness.
View Article and Find Full Text PDFPLoS Pathog
September 2025
Centre for Virus Research, The Westmead Institute for Medical Research, Westmead, Australia.
Dendritic cells (DCs) are potent antigen-presenting cells and play a key role in facilitating the sexual transmission of HIV, functioning as a delivery system responsible for trafficking the virus from exposed barrier sites to their key target cells, CD4 T cells. Although the role of DCs in HIV transmission is well established, the recent advent of high-parameter, single-cell detection technologies, coupled with improved cell isolation techniques, has led to the rapid reclassification of the DC landscape, particularly within human barrier tissues. The identification of new subsets introduces the challenge of incorporating previously understood transmission principles with new, cell-specific, functional nuances to identify the key DCs responsible for facilitating HIV infection.
View Article and Find Full Text PDFCancer Res
September 2025
The Wistar Institute, Philadelphia, PA, United States.
Parkin is a mitochondria-associated E3 ubiquitin (Ub) ligase that mediates mitophagy and organelle quality control. More recently, Parkin has been implicated in stimulating antitumor immunity and reprogramming the tumor immune microenvironment. Here, we showed that Parkin ubiquitinates the alarmin molecule, high mobility group box-1 (HMGB1) on Lys146 (K146) using predominantly K48 linkages.
View Article and Find Full Text PDFAnticancer Drugs
September 2025
Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College.
Nonsmall cell lung cancer (NSCLC) with SMARCA4 deficiency represents a rare subset of lung tumors characterized by early metastasis, poor response to chemotherapy, and unfavorable prognosis. Established therapy strategies for SMARCA4-deficient NSCLC remain elusive. While immune checkpoint inhibitors have been proposed as a potential solution, their efficacy remains uncertain.
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