Dataset Information

Diversity of Dominant Peripheral T Cell Receptor Clone and Soluble Immune Checkpoint Proteins Associated With Clinical Outcomes Following Immune Checkpoint Inhibitor Treatment in Advanced Cancers.

ABSTRACT: Dynamic changes of the peripheral T cell receptor (TCR) and soluble receptors and ligands (sRLs) have the potential to be used as biomarkers to monitor the evolution of the immune system in tumor patients undergoing immunotherapy. These functional biomarkers could be used to predict immune response to treatment with immune checkpoint inhibitors (ICIs) and to provide high-value information on the immune function status of cancer patients, thereby helping physicians to make effective clinical decisions. We collected paired pre- and post-treatment peripheral blood samples from 31 solid tumor patients treated with ICIs. TCR and sRL status were investigated using next-generation sequencing and magnetic bead panels. We found that the diversity of the dominant TCR clone at baseline was correlated with durable clinical benefit in patients receiving single-agent treatment. The D50 index, the diversity from the cumulative 50% of the total complementary determinant region 3, was obtained during treatment. A significant difference in progression-free survival was demonstrated between the D50 high and D50 low groups. This result was validated in an independent cohort. A signature including soluble immune checkpoint proteins (sICPs) was identified. Upregulation of the signature during treatment was correlated with durable clinical benefit. All these results indicate that a novel biomarker based on peripheral TCR and sICPs has the potential to be used in prognostic prediction and for rapid determination of therapeutic outcomes in patients treated with immune checkpoint inhibitors.

SUBMITTER: Li Y

PROVIDER: S-EPMC8216394 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Objective To investigate the clinical features of active tuberculosis (TB) infection due to immune checkpoint inhibitors (ICIs) treatment in patients with advanced cancer. Methods We report the diagnosis and treatment of a case of pulmonary malignancy (squamous cell carcinoma, cT4N3M0 IIIC), secondary to active TB infection following ICIs therapy. Moreover, we summarize and analyze other related cases collected from the China National Knowledge Infrastructure (CNKI), Wanfang Database, PubMed, the Web of Science, and EMBASE (up to October 2021). Results A total of 23 patients, including 20 males and 3 females who were aged 49-87 years with a median age of 65 years, were included in the study. Twenty-two patients were diagnosed by Mycobacterium tuberculosis culture or DNA polymerase chain reaction (PCR), while the remaining patient was diagnosed by tuberculin purified protein derivative and pleural biopsy. One case had an interferon-gamma release assay (IGRA) to rule out latent TB infection prior to the application of ICI. Fifteen patients received an anti-tuberculosis regimen. Among the 20 patients with a description of clinical regression, 13 improved and 7 died. Seven of the patients who improved were treated with ICI again and four of them did not experience a recurrence or worsening of TB. The case diagnosed in our hospital also improved after receiving anti-TB treatment after stopping ICI therapy, and continued chemotherapy on the basis of anti-TB treatment, and his condition is relatively stable at present. Conclusion Due to the lack of specificity of TB infection following ICIs therapy, patients should be followed for fever and respiratory symptoms for 6.3 months after drug administration. It is recommended that IGRA should be performed before ICIs therapy and the development of TB during immunotherapy in patients who are positive in IGRA should be closely monitored. The symptoms of TB in most patients can be improved with ICIs withdrawal and anti-TB treatment, but there is still a need to be alert to the potentially fatal risk of TB.

Project description:ImportanceThe mismatch repair (MMR) pathway plays a crucial role in repairing DNA replication errors in normal and cancer cells. Defects in DNA MMR proteins that determine the microsatellite instability-high (MSI-H) condition lead to the accumulation of mutations and the generation of neoantigens, which may stimulate the antitumor immune response. Clinical trials have demonstrated that MSI-H status is associated with long-term benefit in patients treated with immune checkpoint inhibitors (ICIs).ObjectiveTo evaluate the activity of ICIs in terms of overall response rate (ORR), disease control rate (DCR), overall survival (OS), and progression-free survival (PFS) in patients with MSI-H cancers.Data sourcesPublished articles that evaluated ICIs in the treatment of advanced MSI-H tumors from inception to December 2019 were identified by searching the PubMed, EMBASE, and Cochrane Library databases.Study selectionProspective or retrospective studies, published in the English language, providing outcome data with ICIs in patients with MSI-H cancer were selected.Data extraction and synthesisAuthor and year of publication, type of studies, diseases included, median follow up, type of ICI, median OS ,and PFS, ORR, DCR and 1-, 2-, and 3-year OS were retrieved. Analysis was performed in December 2019.Main outcome and measuresThe primary outcome of interest was ORR. Secondary end points were median PFS, median OS, pooled rate of patients alive at 1, 2 ,and 3 years, and pooled rate of patients that attained disease control rate ([DCR] calculated as the sum of stable disease rate and ORR).ResultsOverall, 939 patients (14 studies) were analyzed mainly in pretreated settings. The pooled ORR was 41.5% (95% CI, 34.9%-48.4%). The pooled DCR was 62.8% (95% CI, 54.5%-70.3%). Pooled median PFS was 4.3 months (95% CI, 3-6.8 months). The pooled median OS was 24 months (95% CI, 20.1-28.5 months). The pooled 1- and 2-year OS were 75.6% (95% CI, 61.8%-85.5%) and 56.5% (95% CI, 46%-66.4%), respectively. Because only 1 study provided 3-year OS data, a formal pooled analysis for 3 years was not possible.Conclusions and relevanceIn this meta-analysis of patients with pretreated MSI-H cancer, ICIs were associated with high activity independent of tumor type and drug used. Among molecular biomarkers for selection of treatment, MMR proteins may have a predictive value for the activity of immunotherapy.

Project description:BackgroundThe advent of immune checkpoint inhibitors (ICIs) therapy has resulted in significant survival benefits in patients with non-small-cell lung cancer (NSCLC) without increasing toxicity. However, the utilisation of immunotherapy for small-cell lung cancer (SCLC) remains unclear, with a scarcity of systematic comparisons of therapeutic effects and safety of immunotherapy in these two major lung cancer subtypes. Herein, we aimed to provide a comprehensive landscape of immunotherapy and systematically review its specific efficacy and safety in advanced lung cancer, accounting for histological types.MethodsWe identified studies assessing immunotherapy for lung cancer with predefined endpoints, including overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and treatment-related adverse events (TRAE), from PubMed, Embase, Medline, and Cochrane library. A random-effects or fixed-effect model was adopted according to different settings.ResultsOverall, 38 trials with 20,173 patients with lung cancer were included in this study. ICI therapy resulted in a significantly prolonged survival in both patients with NSCLC and SCLC when compared with chemotherapy (hazard ratio [HR] = 0.74; 95% confidence interval [CI], 0.70-0.79] and [HR = 0.82; 95% CI, 0.75-0.90], respectively). The magnitude of disease control and survival benefits appeared superior with ICI plus standard of care (SOC) when compared with SOC alone. OS and PFS advantages were observed only when immunotherapy was employed as the first-line treatment in patients with SCLC.ConclusionICI therapy is a promising therapeutic option in patients with NSCLC and SCLC. ICI plus SOC can be recommended as the optimal first-line treatment for patients with SCLC, and double-target ICIs combined with SOC are recommended in patients with NSCLC as both the first and subsequent lines of treatment. Additionally, non-first-line immunotherapy is not recommended in patients with SCLC.

Dataset Information

Diversity of Dominant Peripheral T Cell Receptor Clone and Soluble Immune Checkpoint Proteins Associated With Clinical Outcomes Following Immune Checkpoint Inhibitor Treatment in Advanced Cancers.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets