Nat Med: T cell signatures associated with immune checkpoint blockade toxicity in melanoma patients

Immune checkpoint inhibitors have become the standard treatment for advanced melanoma and have been used as adjuvant therapy after resection for locally advanced melanoma patients, so that patients with advanced melanoma can achieve long-term survival
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Recently, a research article was published in the top medical journal Nature Medicine.
In this study, the researchers used time-of-flight mass spectrometry, single-cell RNA-sequencing, single-cell V(D)J sequencing, bulk RNA sequencing, and bulk T cell stimulation.
Peripheral blood samples from melanoma patients treated with PD-1 monotherapy or anti-PD-1 and anti-CTLA-4 in combination with immune checkpoint inhibitors were investigated
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By analyzing 93 blood samples before and early treatment with immune checkpoint inhibitors and 3 patient cohorts (n=27, 26 and 18), the researchers identified 2 pre-treatment factors in the circulation—activated CD4 positivity Memory T cell abundance and TCR diversity—associated with the development of serious immune-related adverse events, regardless of organ system involvement
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The researchers also explored treatment changes in TCR clonality in melanoma patients receiving combination therapy and correlated the study's findings with the severity and timing of onset of immune-related adverse events
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These results demonstrate a circulating T cell signature associated with immune checkpoint inhibitor-induced toxicity, which has important implications for improving clinical diagnosis and treatment of melanoma .

Original source:

Alexander X.