TCR Repertoire as a Novel Indicator for Immune Monitoring and Prognosis Assessment of Patients With Cervical Cancer

Abstract

There is increasing evidence that deep sequencing-based T cell repertoire can sever as a biomarker of immune response in cancer patients; however, the characteristics of T cell repertoire including diversity and similarity, as well as its prognostic significance in patients with cervical cancer (CC) remain unknown. In this study, we applied a high throughput T cell receptor (TCR) sequencing method to characterize the T cell repertoires of peripheral blood samples from 25 CC patients, 30 cervical intraepithelial neoplasia (CIN) patients and 20 healthy women for understanding the immune alterations during the cervix carcinogenesis. In addition, we also explored the signatures of TCR repertoires in the cervical tumor tissues and paired sentinel lymph nodes from 16 CC patients and their potential value in predicting the prognosis of patients. Our results revealed that the diversity of circulating TCR repertoire gradually decreased during the cervix carcinogenesis and progression, but the circulating TCR repertoires in CC patients were more similar to CIN patients than healthy women. Interestingly, several clonotypes uniquely detected in CC patients tended to share similar CDR3 motifs, which differed from those observed in CIN patients. In addition, the TCR repertoire diversity in sentinel lymphatic nodes from CC patients was higher than in tumor tissues. More importantly, less clonotypes in TCR repertoire of sentinel lymphatic node was associated with the poor prognosis of the patients. Overall, our findings suggested that TCR repertoire might be a potential indicator of immune monitoring and a biomarker for predicting the prognosis of CC patients. Although functional studies of T cell populations are clearly required, this study have expanded our understanding of T cell immunity during the development of CC and provided an experimental basis for further studies on its pathogenesis and immunotherapy.

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

“…Such impact has not been seen for OS, probably due to the small size of the cohort, but when we separated patients according to their early death or long survival, a significant association is visible, with a lower DR in patients who died early. In line with our data, in many tumor types, TCR repertoire diversity appears as a prognostic factor of clinical outcome in cancer patient, a high diversity being associated with a better prognosis (Cui et al, ; Jin et al, ; Keane et al, ; Lin et al, ; Manuel et al, ; Tamura et al, ). A high TCR repertoire diversity could reflect a good functionality of the immune system, increasing chances that a sub‐population immunologically pertinent should be present, leading therefore to a better anti‐tumor immune response.…”

“…In nasopharyngeal carcinoma, a lower diversity of TCR repertoire in tumors compared to paired tissues and a higher diversity in peripheral blood are associated with a poor prognosis (Jin et al, ). The diversity of circulating TCR repertoire is gradually decreasing during tumor progression in patients with cervical cancer (Cui et al, ). Elsewhere, high dominant clones within tumor microenvironment were associated with poor outcome in diffuse large B‐cell lymphoma (Keane et al, ).…”

T cell receptor repertoire as a prognosis marker for heat shock protein peptide complex-96 vaccine trial against newly diagnosed glioblastoma

“…31,32 This implies that a preexisting T-cell-mediated immune response, reflected by local intratumoral TCR clonal expansion, would be a pre-requisite for successful treatment outcomes to these immunotherapies. In contrast, several studies have observed an opposite direction of the association between TCR repertoire diversity and treatment outcomes in other solid tumor types, 33,34 underscoring the complex interactions between the immune system and advanced malignancies. 35 This complexity notwithstanding, these reports also suggest the direct measurement of TCR repertoire diversity within tumors may be utilized to predict clinical immunotherapeutic efficacy.…”

Inference and effects of barcode multiplets in droplet-based single-cell assays

“…As single-cell approaches move toward the precise quantification of rare cell types, trajectories, perturbations, and clones, an understanding of potential artifacts is essential as their confounding effects may become exacerbated in large datasets. Additionally, as these measurements move toward clinical applications 9 , particularly in tumors where TCR repertoire may serve as a prognostic biomarker 10 , barcode multiplets may significantly confound interpretation. In some analyses (with <15% clones), we anticipate that many identified clonal cells may arise from bead multiplets.…”