T‐cell receptor diversity as a prognostic biomarker in melanoma patients

Abstract

There is increasing evidence that T‐cell receptor (TCR) repertoire diversity can be a predictive biomarker of immune responses in cancer patients. However, the characteristics of the T‐cell repertoire together with its prognostic significance in melanoma patients and impact on disease progression remain unknown. We investigated the combinatorial TCR repertoire diversity by semi‐quantitative multi‐N‐plex PCR in peripheral blood samples from 44 melanoma patients together with seven matched metastatic lymph nodes and explored its potential predictive value on clinical prognosis. The diversity was quantified by calculating both richness (number of different specificities) and evenness (relative abundance of the different specificities). Our results revealed that a higher TCR repertoire diversity in blood of patients was associated with a longer PFS, while divpenia (low repertoire diversity) was linked with poor prognosis. The diversity was significantly higher in patients undergoing late relapse and long survival compared to patients who progressed rapidly. Interestingly, the TCR repertoire diversity in tumor may have a potential prognostic value. Thus, our study highlights that the TCR repertoire diversity is a prognostic indicator of clinical outcome in patients with melanoma.

Prognostic value and peripheral immunologic correlates of early FDG PET response imaging in a phase II trial of risk-adaptive chemoradiation for unresectable non-small cell lung cancer

“…A recent report by Shahamatdar et al 46 analyzing germline variants in the TCGA cohort demonstrated that host genetics are associated with phenotypes that describe the immune component of the tumor microenvironment; they found one SNP associated with the amount of infiltrating follicular helper T cells; and 23 candidate genes, some of which are involved in cytokine-mediated signaling. Our patient cohort supports prior findings that patients with greater TCR richness in the peripheral blood had improved survival compared with patients with less clonal richness 47-49 . TCR richness declined with chemoradiation although a smaller mid-treatment decline in TCR diversity was associated with improved survival.…”

Prognostic Value of Early Fluorodeoxyglucose-Positron Emission Tomography Response Imaging and Peripheral Immunologic Biomarkers: Substudy of a Phase II Trial of Risk-Adaptive Chemoradiation for Unresectable Non-Small Cell Lung Cancer

“…A recent report by Shahamatdar et al 46 analyzing germline variants in the TCGA cohort demonstrated that host genetics are associated with phenotypes that describe the immune component of the tumor microenvironment; they found one SNP associated with the amount of infiltrating follicular helper T cells; and 23 candidate genes, some of which are involved in cytokinemediated signaling. Our patient cohort supports prior findings that patients with greater TCR richness in the peripheral blood had improved survival compared with patients with less clonal richness [47][48][49] . TCR richness declined with chemoradiation although a smaller mid-treatment decline in TCR diversity was associated with improved survival.…”

“…Our patient cohort supports prior findings that patients with greater TCR richness in the peripheral blood had improved survival compared with patients with less clonal richness. 46 , 47 , 48 TCR richness declined with chemoradiation although a smaller midtreatment decline in TCR diversity was associated with improved survival. Pretreatment TCR clone distribution slope, among other diversity metrics, was correlated with PET response status, but none of the TCR diversity metrics were correlated with midtreatment residual TLG.…”

Immune Equilibrium Depends on the Interaction Between Recognition and Presentation Landscapes

“…Probably, homeostatic proliferation can also contribute to a decrease in the general diversity of TCRs and the TCR diversity of naïve T cells with age (23), which negatively affects the protective function of the immune system against infections or other antigenic challenges in senior age (23,164). It was shown that increased sensitivity to viral and oncological disease was associated with a decrease in the diversity of TCRs and connected with the formation of holes in the TCR repertoires (164)(165)(166)(167).…”