Objective: Although several studies have found dietary intake is related to multiple myeloma (MM) and its precursor status risks, the role of one’s nutritional status has been ignored and its role in plasma cell neoplasm development is still unclear. This study aimed to explore the relationship between various clinical indices of nutritional status and the risk of monoclonal gammopathy of undetermined significance (MGUS) in the population. Methods: We selected 9520 participants from the NHANES III and NHANES 1999–2004 studies. Controlling nutritional status index (CONUT), prognostic nutritional index (PNI), geriatric nutritional risk index (GNRI) and body mass index (BMI) were calculated as indices of nutritional status of the participants. Associations between nutritional indices and MGUS were investigated using multiple logistic regression, subgroup analysis, and an RCS model. Results: In our study, 266 participants had MGUS, with a prevalence of 2.79%. This study found that CONUT and PNI identified populations with poor nutritional status and had a significant positive correlation with the risk of MGUS. In multivariate logistic regression, compared with the lower CONUT score (<3) group, the OR for the group with higher scores (≥3) was 1.805 (95%CI: 1.271, 2.564). Compared with the lowest quartile group, the highest quartile PNI score group had an OR of 0.509 (95%CI: 0.290, 0.896). GNRI had no significant correlation with the risk of MGUS, with an OR of 0.737 (95%CI: 0.443, 1.227). Conclusion: This study found that older adults with CONUT and PNI scores indicating poorer nutrition had a higher risk of MGUS.

Metabolic disorders mediated chimeric antigen receptor - T cell (CAR-T) exhaustion impaired cancer immunotherapy. Endogenous sulfur dioxide (SO₂) derived from L-cysteine catalysis regulated immune cell functions. However, its role in CAR-T cell exhaustion remained unknown. In this study, we identified that SO₂ accumulated in the bone marrow microenvironment of relapsed multiple myeloma patients inhibited CD8⁺ T cell and CAR-T cell infiltration and promoted a transcriptional profile consistent with functional exhaustion, leading to impaired antitumor immunity. Tumor cell derived SO₂ altered mitochondrial morphology and disrupted mitochondrial membrane potential in CAR-T cells, accompanied by impaired cytokine secretion and loss of cytotoxic function. Mechanistically, SO₂ enhanced interaction of dynamin-related protein 1 (DRP1) and voltage-dependent anion channel 1 and mitochondrial fission via DRP1 sulphenylation at cysteine 607 (Cys607), with abnormal increases in DRP1 GTPase activity, disrupting mitochondrial integrity. Site mutation of Cys607 in CAR-T cells abrogated DRP1 sulphenylation and restored mitochondrial structure and improves antitumor immunity. These findings define a novel redox-mediated mechanism of mitochondrial dysfunction in CAR-T cells exhaustion and identify the SO₂-DRP1 axis as a potential therapeutic target to overcome metabolic exhaustion in CAR-T cell therapy.

Messenger RNA (mRNA) therapeutics have evolved from a technically constrained modality into a clinically validated platform for vaccination that is increas