Peripheral blood T-cell receptor repertoire as a predictor of clinical outcomes in gastrointestinal cancer patients treated with PD-1 inhibitor

Ji, Sunhee; Li, J; Chang, Liisa; Zhao, Chuanhua; Jia, Ru; Tan, Zhao-Li; Liu, R; Zhang, Y; Li, Y; Yin, Guang; Guan, Yanfang; Xia, Xuefeng; Yi, Xiaohui; Xu, Jianming

doi:10.1007/s12094-021-02562-4

Cited by 14 publications

(13 citation statements)

References 40 publications

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“…A similar study in melanoma patients observed that high pre-therapy clonality was associated with poor response to CTLA4, whereas it predicted good response to PD1 blockade ( 50 ). Higher baseline TCR diversity has been found to correlate with better disease control in patients with gastrointestinal cancers ( 51 ) and relapsed/refractory classical Hodgkin Lymphoma ( 52 ) receiving anti-PD1 therapy. Similarly, low T-cell clonality prior to anti-PD-L1 therapy and its increase in the periphery after immunotherapy has been associated with clinical benefits in patients with metastatic urothelial cancer ( 53 ).…”

Section: Impact Of Thymic Function and Tcr Diversity In Clinical Conditionsmentioning

confidence: 99%

Thymic Function and T-Cell Receptor Repertoire Diversity: Implications for Patient Response to Checkpoint Blockade Immunotherapy

Cardinale¹,

Compagnucci²,

Locatelli³

et al. 2021

Front. Immunol.

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The capacity of T cells to recognize and mount an immune response against tumor antigens depends on the large diversity of the T-cell receptor (TCR) repertoire generated in the thymus during the process of T-cell development. However, this process is dramatically impaired by immunological insults, such as that caused by cytoreductive cancer therapies and infections, and by the physiological decline of thymic function with age. Defective thymic function and a skewed TCR repertoire can have significant clinical consequences. The presence of an adequate pool of T cells capable of recognizing specific tumor antigens is a prerequisite for the success of cancer immunotherapy using checkpoint blockade therapy. However, while this approach has improved the chances of survival of patients with different types of cancer, a large proportion of them do not respond. The limited response rate to checkpoint blockade therapy may be linked to a suboptimal TCR repertoire in cancer patients prior to therapy. Here, we focus on the role of the thymus in shaping the T-cell pool in health and disease, discuss how the TCR repertoire influences patients’ response to checkpoint blockade therapy and highlight approaches able to manipulate thymic function to enhance anti-tumor immunity.

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Section: Impact Of Thymic Function and Tcr Diversity In Clinical Conditionsmentioning

confidence: 99%

Thymic Function and T-Cell Receptor Repertoire Diversity: Implications for Patient Response to Checkpoint Blockade Immunotherapy

Cardinale¹,

Compagnucci²,

Locatelli³

et al. 2021

Front. Immunol.

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show abstract

“…In sum, this analysis demonstrates the similarity between TRegs and TConvs when analyzing their diversity features, and it portrays how these features can be predictive when analyzing TCR repertoires of breast cancer. Many studies–to cite a few, [ 2 , 51 , 52 ], and [ 53 ]–have opted to explore TCR repertoires in their diversity dimension (specifically, the Shannon index). In corroboration with our results, diversity is an essential feature for TCR repertoire analyses and should not be omitted from any relevant discussion.…”

Section: Resultsmentioning

confidence: 99%

GENTLE: a novel bioinformatics tool for generating features and building classifiers from T cell repertoire cancer data

et al. 2023

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Background In the global effort to discover biomarkers for cancer prognosis, prediction tools have become essential resources. TCR (T cell receptor) repertoires contain important features that differentiate healthy controls from cancer patients or differentiate outcomes for patients being treated with different drugs. Considering, tools that can easily and quickly generate and identify important features out of TCR repertoire data and build accurate classifiers to predict future outcomes are essential. Results This paper introduces GENTLE (GENerator of T cell receptor repertoire features for machine LEarning): an open-source, user-friendly web-application tool that allows TCR repertoire researchers to discover important features; to create classifier models and evaluate them with metrics; and to quickly generate visualizations for data interpretations. We performed a case study with repertoires of TRegs (regulatory T cells) and TConvs (conventional T cells) from healthy controls versus patients with breast cancer. We showed that diversity features were able to distinguish between the groups. Moreover, the classifiers built with these features could correctly classify samples (‘Healthy’ or ‘Breast Cancer’)from the TRegs repertoire when trained with the TConvs repertoire, and from the TConvs repertoire when trained with the TRegs repertoire. Conclusion The paper walks through installing and using GENTLE and presents a case study and results to demonstrate the application’s utility. GENTLE is geared towards any researcher working with TCR repertoire data and aims to discover predictive features from these data and build accurate classifiers. GENTLE is available on https://github.com/dhiego22/gentle and https://share.streamlit.io/dhiego22/gentle/main/gentle.py.

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“…Clonality and diversity of intratumoral and peripheral TCR repertoire have also recently emerged as potential markers of responsiveness to immune checkpoint inhibitors in multiple cancer settings including melanoma [ 178 , 179 , 180 , 181 , 182 , 183 , 184 , 185 ]. Overall, these studies suggest that patients who exhibit a higher diversity of TCR repertoire before treatment and early evolution of the T cell populations after treatment start have a greater chance to benefit from immunotherapy.…”

Section: Biomarkers Of Immunotherapy Response/resistance In Melanomamentioning

confidence: 99%

Shaping the Future of Immunotherapy Targets and Biomarkers in Melanoma and Non-Melanoma Cutaneous Cancers

Spiliopoulou

Vornicova

Genta

et al. 2023

IJMS

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Recent advances in treating cutaneous melanoma have resulted in impressive patient survival gains. Refinement of disease staging and accurate patient risk classification have significantly improved our prognostic knowledge and ability to accurately stratify treatment. Undoubtedly, the most important step towards optimizing patient outcomes has been the advent of cancer immunotherapy, in the form of immune checkpoint inhibition (ICI). Immunotherapy has established its cardinal role in the management of both early and late-stage melanoma. Through leveraging outcomes in melanoma, immunotherapy has also extended its benefit to other types of skin cancers. In this review, we endeavor to summarize the current role of immunotherapy in melanoma and non-melanoma skin cancers, highlight the most pertinent immunotherapy-related molecular biomarkers, and lastly, shed light on future research directions.

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Peripheral blood T-cell receptor repertoire as a predictor of clinical outcomes in gastrointestinal cancer patients treated with PD-1 inhibitor

Cited by 14 publications

References 40 publications

Thymic Function and T-Cell Receptor Repertoire Diversity: Implications for Patient Response to Checkpoint Blockade Immunotherapy

Thymic Function and T-Cell Receptor Repertoire Diversity: Implications for Patient Response to Checkpoint Blockade Immunotherapy

GENTLE: a novel bioinformatics tool for generating features and building classifiers from T cell repertoire cancer data

Shaping the Future of Immunotherapy Targets and Biomarkers in Melanoma and Non-Melanoma Cutaneous Cancers

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