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T cell receptor clonotype diversity in breast cancer patients at various stages and ages

Kornelia Polyak, Ludwig Cancer Research
Kornelia Polyak

Researchers led in part by Ludwig Harvard’s Kornelia Polyak studied the diversity of the T cell receptor (TCR) clonotypes—a unique nucleotide sequence that arises during the gene rearrangement process for the TCR—in the peripheral blood of 485 breast cancer patients diagnosed with ductal carcinoma in situ (DCIS) or de novo stage IV disease before or after age 45. The tumor immune landscape in patients changes as they progress through the stages of breast cancer, from ductal hyperplasia to metastatic disease, and Kornelia and her colleagues have previously described increasing immunosuppression and decreasing TCR clonotype diversity in the tumor microenvironment during disease progression. There is, however, also growing evidence to suggest that TCR clonotype diversity of circulating T cells—a quantitative measure of immune health that seems to decrease with age—might similarly influence disease progression and anti-tumor immunity. Kornelia and colleagues reported in PNAS in November that such “peripheral” TCR clonotype diversity is lower in older patients regardless of disease stage, and in younger patients with advanced disease compared to those with DCIS. Notably, in older patients, those with DCIS and a higher peripheral clonotype diversity were more likely to suffer a relapse. The findings underscore the importance of peripheral immunity and age in disease progression and the authors suggest peripheral TCR clonotype diversity should be further explored in large clinical studies as a biomarker for disease progression.

Peripheral blood TCR clonotype diversity as an age-associated marker of breast cancer progression
PNAS, 2023 November 27

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