Molecular T-Cell Repertoire Analysis as Source of Prognostic and Predictive Biomarkers for Checkpoint Blockade Immunotherapy

Aversa, Ilenia; Malanga, Donatella; Fiume, Giuseppe; Palmieri, Camillo

doi:10.3390/ijms21072378

Cited by 49 publications

(54 citation statements)

References 95 publications

(130 reference statements)

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“…In line with low T cell clonality generally indicating a lack of T cell expansion and a suppressed T cell repertoire 28 , T cell clonality showed significantly positive correlation with the frequency of the most dominant T cell clones in these IPNs (Supplementary Fig. 9a-d), suggesting higher T cell clonality was associated with increased clonal expansion.…”

Section: Resultsmentioning

confidence: 61%

Immune evolution from preneoplasia to invasive lung adenocarcinomas and underlying molecular features

Dejima

Chen

et al. 2021

Nat Commun

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The mechanism by which anti-cancer immunity shapes early carcinogenesis of lung adenocarcinoma (ADC) is unknown. In this study, we characterize the immune contexture of invasive lung ADC and its precursors by transcriptomic immune profiling, T cell receptor (TCR) sequencing and multiplex immunofluorescence (mIF). Our results demonstrate that anti-tumor immunity evolved as a continuum from lung preneoplasia, to preinvasive ADC, minimally-invasive ADC and frankly invasive lung ADC with a gradually less effective and more intensively regulated immune response including down-regulation of immune-activation pathways, up-regulation of immunosuppressive pathways, lower infiltration of cytotoxic T cells (CTLs) and anti-tumor helper T cells (Th), higher infiltration of regulatory T cells (Tregs), decreased T cell clonality, and lower frequencies of top T cell clones in later-stages. Driver mutations, chromosomal copy number aberrations (CNAs) and aberrant DNA methylation may collectively impinge host immune responses and facilitate immune evasion, promoting the outgrowth of fit subclones in preneoplasia into dominant clones in invasive ADC.

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Section: Resultsmentioning

confidence: 61%

Immune evolution from preneoplasia to invasive lung adenocarcinomas and underlying molecular features

Dejima

Chen

et al. 2021

Nat Commun

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“…The diversity and clonality of neoantigen-responsive TCR are also potential biomarkers for immunotherapy ( 95 , 96 ). Additional research studies in this topic will aid the successful application of immunotherapy.…”

Section: The Role Of Tnb In Tumor Immunotherapy and Other Therapiesmentioning

confidence: 99%

Beyond Tumor Mutation Burden: Tumor Neoantigen Burden as a Biomarker for Immunotherapy and Other Types of Therapy

2021

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Immunotherapy has significantly improved the clinical outcome of patients with cancer. However, the immune response rate varies greatly, possibly due to lack of effective biomarkers that can be used to distinguish responders from non-responders. Recently, clinical studies have associated high tumor neoantigen burden (TNB) with improved outcomes in patients treated with immunotherapy. Therefore, TNB has emerged as a biomarker for immunotherapy and other types of therapy. In the present review, the potential application of TNB as a biomarker was evaluated. The methods of neoantigen prediction were summarized and the mechanisms involved in TNB were investigated. The impact of high TNB and increased number of infiltrating immune cells on the efficacy of immunotherapy was also addressed. Finally, the future challenges of TNB were discussed.

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“…Studies in various tumors have investigated whether peripheral TCR repertoire analysis could serve as a predictive biomarker of response to immunotherapy (54)(55)(56)(57)(58). However, the predictive value of the peripheral TCR repertoire remains controversial, likely because the existence of non-tumor-specific TCRs in PBMCs diluted tumor neoantigen-specific TCRs (59).…”

Section: T Cell Receptor Repertoirementioning

confidence: 99%

Emerging Blood-Based Biomarkers for Predicting Response to Checkpoint Immunotherapy in Non-Small-Cell Lung Cancer

Zhang

Pang

et al. 2020

Front. Immunol.

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Immune checkpoint inhibitors (ICIs) have brought impressive clinical benefits in a variety of malignancies over the past years, which dramatically revolutionized the cancer treatment paradigm. Monotherapy or in combination with chemotherapy of ICIs targeting programmed death 1/programmed death ligand 1 (PD-L1) has emerged as an alternative treatment for patients with advanced non-small-cell lung cancer (NSCLC). However, constrained by primary or acquired resistance, most patients obtain limited benefits from ICIs and occasionally suffer from severe immune-related adverse events. Moreover, owing to the complexity of the tumor microenvironment and the technical limitations, clinical application of PD-L1 and tumor mutation burden as biomarkers shows many deficiencies. Thus, additional predictive biomarkers are required to further advance the precision of proper patient selection, avoiding the exposure of potential nonresponders to unnecessary immunotoxicity. Nowadays, an increasing number of investigations are focusing on peripheral blood as a noninvasive alternative to tissue biopsy in predicting and monitoring treatment outcomes. Herein, we summarize the emerging blood-based biomarkers that could predict the clinical response to checkpoint immunotherapy, specifically in patients with NSCLC.

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Molecular T-Cell Repertoire Analysis as Source of Prognostic and Predictive Biomarkers for Checkpoint Blockade Immunotherapy

Cited by 49 publications

References 95 publications

Immune evolution from preneoplasia to invasive lung adenocarcinomas and underlying molecular features

Immune evolution from preneoplasia to invasive lung adenocarcinomas and underlying molecular features

Beyond Tumor Mutation Burden: Tumor Neoantigen Burden as a Biomarker for Immunotherapy and Other Types of Therapy

Emerging Blood-Based Biomarkers for Predicting Response to Checkpoint Immunotherapy in Non-Small-Cell Lung Cancer

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