{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T20:05:20Z","timestamp":1767902720128,"version":"3.49.0"},"reference-count":21,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,9,17]],"date-time":"2024-09-17T00:00:00Z","timestamp":1726531200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Broad T cell phenotypic alterations and potential dysfunctions were prominent in COVID-19. There are few and inconclusive data about the role of immune checkpoints for T cell exhaustion\/activation during SARS-CoV-2 infection in multiple myeloma (MM) patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We tested T cell subsets and immune checkpoints in 177 MM patients with COVID-19, as well as in 32 healthy infected controls and 42 uninfected MM patients. The percentage of CD4+ and CD8+ subpopulation and immune checkpoints (PD-1, TIGIT, TIM-3, LAG-3, CTLA-4, OX40, and 4-1BB) were evaluated by flow cytometry.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We have found that pronounced lymphopenia and inverted CD4\/CD8 ratio in severe COVID-19 patients were especially developed within the first month after infection. And T cell subset dysregulation was persistent in severe patients recovering from SARS-CoV-2 infection. Immune checkpoints on CD4+ T cells were variable and uncorrelated with the level of adaptive immunity, while the proportion of CD4+ T cells was positively correlated with humoral immune response. PD-1 and TIGIT on CD8+ T cells were significantly elevated in severe patients and sustained for more than 2 months, which was associated with impaired cellular immune function. Moreover, exhausted molecules PD-1 and TIGIT on T cells were reduced in immunotherapy patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The prolonged T cell dysregulation after severe SARS-CoV-2 infection highlights the close surveillance from reinfection in MM patients even during convalescence. PD-1 and TIGIT on CD8+ T cells could be important prognostic factors to stratify prognosis in MM patients with COVID-19. Moreover, immunotherapy may downregulate the expression of exhausted checkpoints PD-1 and TIGIT, leading to T cell overactivation and severe COVID-19.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2024.1448653","type":"journal-article","created":{"date-parts":[[2024,9,18]],"date-time":"2024-09-18T12:24:48Z","timestamp":1726662288000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Identifying immune checkpoints on dysregulated T-cells as prognostic biomarkers for multiple myeloma patients with 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