Characteristics and significance of peripheral blood T-cell receptor repertoire features in patients with indeterminate lung nodules.
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ABSTRACT:
SUBMITTER: Luo H
PROVIDER: S-EPMC9548502 | biostudies-literature | 2022 Oct
REPOSITORIES: biostudies-literature
Publications
Characteristics and significance of peripheral blood T-cell receptor repertoire features in patients with indeterminate lung nodules.
Luo Huaichao H Zu Ruiling R Huang Ziru Z Li Yingqiang Y Liao Yulin Y Luo Wenxin W Zhou Peng P Wang Dongsheng D Chen Shifu S Li Weimin W Huang Jian J
Signal transduction and targeted therapy 20221010 1
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Project description:BackgroundThe clinical significance of indeterminate pulmonary nodules (IPN) in patients with resectable pancreatic adenocarcinoma (PDAC) is unknown. The rate of detection on IPN has risen due to enhanced staging investigations to determine resectability. IPNs detected on preoperative imaging represent a clinical dilemma and complicate decision-making. Currently, there are no recommendations on the management of IPN. This review provides a comprehensive overview of the current knowledge on the natural history of IPN detected among patients with resectable PDAC.MethodsA systematic review based on a search in Medline and Embase databases was performed. All clinical studies evaluating the significance of IPN in patients with resectable PDAC were included. PRISMA guidelines were followed.ResultsFive studies met the inclusion criteria. The total patient population was 761. The prevalence of IPN reported ranged from 18 to 71%. The median follow-up duration was 17 months. The median overall survival was 19 months. Patients with pre-operative IPN which subsequently progressed to clinically recognizable pulmonary metastases, ranged from 1.5 to 16%. Four studies found that there was no significant difference in median overall survival in patients with or without IPNs.ConclusionThis is a first review on the significance of IPN in patients with resectable PDAC. The preoperative presence of IPN does not demonstrate an association with overall survival after surgery. The identification of IPN is a significant finding however it should not preclude patients with resectable PDAC from undergoing curative resection.
| S-EPMC8106596 | biostudies-literature
Project description:Several studies have demonstrated that the T-cell receptor (TCR) repertoire is associated with prognosis and immune therapy response in several types of cancer. However, the comprehensive features of TCR repertoire in tumor-infiltrating and circulating T cells, as well as its clinical significance of diagnosis in hepatocellular carcinoma (HCC) patients, are still unknown. In this study, we perform paired tumor/peritumoral tissues and peripheral blood samples from 58 patients with HCC and sequenced them with high-throughput TCR to comprehensively analyze the characteristics of TCR and the clinical significance of peripheral TCR sequence. By exploring the abundance and diversity of TCR repertoires, we observe that there was a significantly higher TCR diversity in peripheral blood than in tumoral and peritumoral tissues, while tumoral and peritumoral tissues showed similar TCR diversity. A substantial difference in the usage frequencies of several Vβ, Jβ genes, and TCRβ VJ pairings was found among three types of tissues. Moreover, we reveal that HCC patients have a unique profile of TCR repertoire in peripheral blood in contrast to healthy individuals. We further establish an HCC diagnostic model based on TCRβ VJ pairing usage in peripheral blood, which yields a best-fit area under the curve (AUC) of 0.9746 ± 0.0481 (sensitivity = 0.9675 ± 0.0603, specificity = 0.9998 ± 0.0007, average of 100 repeats) in the test set. Our study describes the characteristics of tissue infiltration and circulating T-cell bank in patients with HCC and shows the potential of using circulating TCR sequence as a biomarker for the non-invasive diagnosis of patients with HCC.
| S-EPMC8965762 | biostudies-literature
Project description: Not available
| S-EPMC7365373 | biostudies-literature
Project description:Evaluation of indeterminate pulmonary nodules is a complex challenge. Most are benign but frequently undergo invasive and costly procedures to rule out malignancy. A plasma protein classifier was developed that identifies likely benign nodules that can be triaged to CT surveillance to avoid unnecessary invasive procedures. The clinical utility of this classifier was assessed in a prospective-retrospective analysis of a study enrolling 475 patients with nodules 8-30 mm in diameter who had an invasive procedure to confirm diagnosis at 12 sites. Using this classifier, 32.0 % (CI 19.5-46.7) of surgeries and 31.8 % (CI 20.9-44.4) of invasive procedures (biopsy and/or surgery) on benign nodules could have been avoided. Patients with malignancy triaged to CT surveillance by the classifier would have been 24.0 % (CI 19.2-29.4). This rate is similar to that described in clinical practices (24.5 % CI 16.2-34.4). This study demonstrates the clinical utility of a non-invasive blood test for pulmonary nodules.
| S-EPMC4651976 | biostudies-literature
Project description:BackgroundNon-invasive biomarkers are needed to improve management of indeterminate pulmonary nodules (IPNs) suspicious for lung cancer.MethodsProtein biomarkers were quantified in serum samples from patients with 6-30 mm IPNs (n = 338). A previously derived and validated radiomic score based upon nodule shape, size, and texture was calculated from features derived from CT scans. Lung cancer prediction models incorporating biomarkers, radiomics, and clinical factors were developed. Diagnostic performance was compared to the current standard of risk estimation (Mayo). IPN risk reclassification was determined using bias-corrected clinical net reclassification index.ResultsAge, radiomic score, CYFRA 21-1, and CEA were identified as the strongest predictors of cancer. These models provided greater diagnostic accuracy compared to Mayo with AUCs of 0.76 (95 % CI 0.70-0.81) using logistic regression and 0.73 (0.67-0.79) using random forest methods. Random forest and logistic regression models demonstrated improved risk reclassification with median cNRI of 0.21 (Q1 0.20, Q3 0.23) and 0.21 (0.19, 0.23) compared to Mayo for malignancy.ConclusionsA combined biomarker, radiomic, and clinical risk factor model provided greater diagnostic accuracy of IPNs than Mayo. This model demonstrated a strong ability to reclassify malignant IPNs. Integrating a combined approach into the current diagnostic algorithm for IPNs could improve nodule management.
| S-EPMC10057862 | biostudies-literature
Project description:BackgroundIdentifying a circulating biomarker predictive of immune checkpoint inhibitor (ICI) benefit in patients with small cell lung cancer (SCLC) remains an unmet need. Characteristics of peripheral and intratumoral T-cell receptor (TCR) repertoires have been shown to predict clinical outcomes in non-small cell lung cancer (NSCLC). Recognizing a knowledge gap, we sought to characterize circulating TCR repertoires and their relationship with clinical outcomes in SCLC.MethodsSCLC patients with limited (n=4) and extensive (n=10) stage disease were prospectively enrolled for blood collection and chart review. Targeted next-generation sequencing of TCR beta and alpha chains of peripheral blood samples was performed. Unique TCR clonotypes were defined by identical CDR3, V gene, and J gene nucleotide sequences of the beta chain and subsequently used to calculate TCR diversity indices.ResultsPatients with stable versus progressive and limited versus extensive stage disease did not demonstrate significant differences in V gene usage. Kaplan-Meier curve and log-rank analysis did not identify a statistical difference in progression-free survival (PFS) (P=0.900) or overall survival (OS) (P=0.200) between high and low on-treatment TCR diversity groups, although the high diversity group exhibited a trend toward increased OS.ConclusionsWe report the second study investigating peripheral TCR repertoire diversity in SCLC. With a limited sample size, no statistically significant associations between peripheral TCR diversity and clinical outcomes were observed, though further study is warranted.
| S-EPMC9989808 | biostudies-literature
Project description:BackgroundIn the context of breast cancer (BC), the correlation between lymphocytes and clinical outcomes, along with treatment response, has garnered attention. Despite this, few investigations have delved into the interplay among distinct peripheral blood lymphocyte (PBL) types, immune attributes, and their clinical implications within the BC landscape.MethodsThe primary objective of this study was to scrutinize the baseline status of PBL subsets in patients with primary BC, track their dynamic changes throughout treatment, and ascertain their interrelation with prognosis. Flow cytometry was employed to analyse PBLs from a cohort of 74 BC patients.ResultsOur analysis revealed that baseline levels of Treg and PD-L1 + T cells were lower in BC patients compared to the reference values. Notably, a disparity in baseline PD-L1 + T cell levels surfaced between patients who underwent adjuvant therapy and those subjected to neoadjuvant therapy (NAT). Furthermore, a meticulous evaluation of PBL subsets before and after treatment underscored discernible alterations in 324 + T cells and CD19 + CD32 + B cells over the course of therapy. Strikingly, heightened CD4 + T cell levels at baseline were linked to enhanced event-free survival (EFS) (p = 0.02) and a robust response to chemotherapy.ConclusionsThese results indicate that PBLs may serve as a significant marker to assess the immune status of BC patients, and therapy has the potential to modify patient immune profiles. In addition, peripheral blood CD4 + T cell levels may serve as promising biomarkers for diagnosis and prognosis in future studies of BC.
| S-EPMC10775541 | biostudies-literature
Project description:BackgroundRadiomics, defined as quantitative features extracted from images, provide a non-invasive means of assessing malignant versus benign pulmonary nodules. In this study, we evaluate the consistency with which perinodular radiomics extracted from low-dose computed tomography images serve to identify malignant pulmonary nodules.Materials and methodsUsing the National Lung Screening Trial (NLST), we selected individuals with pulmonary nodules between 4mm to 20mm in diameter. Nodules were segmented to generate four distinct datasets; 1) a Tumor dataset containing tumor-specific features, 2) a 10 mm Band dataset containing parenchymal features between the segmented nodule boundary and 10mm out from the boundary, 3) a 15mm Band dataset, and 4) a Tumor Size dataset containing the maximum nodule diameter. Models to predict malignancy were constructed using support-vector machine (SVM), random forest (RF), and least absolute shrinkage and selection operator (LASSO) approaches. Ten-fold cross validation with 10 repetitions per fold was used to evaluate the performance of each approach applied to each dataset.ResultsWith respect to the RF, the Tumor, 10mm Band, and 15mm Band datasets achieved areas under the receiver-operator curve (AUC) of 84.44%, 84.09%, and 81.57%, respectively. Significant differences in performance were observed between the Tumor and 15mm Band datasets (adj. p-value <0.001). However, when combining tumor-specific features with perinodular features, the 10mm Band + Tumor and 15mm Band + Tumor datasets (AUC 87.87% and 86.75%, respectively) performed significantly better than the Tumor Size dataset (66.76%) or the Tumor dataset. Similarly, the AUCs from the SVM and LASSO were 84.71% and 88.91%, respectively, for the 10mm Band + Tumor.ConclusionsThe combined 10mm Band + Tumor dataset improved the differentiation between benign and malignant lung nodules compared to the Tumor datasets across all methodologies. This demonstrates that parenchymal features capture novel diagnostic information beyond that present in the nodule itself. (data agreement: NLST-163).
| S-EPMC9895123 | biostudies-literature
Project description:Purpose18F-FDG PET/CT is widely used to evaluate indeterminate pulmonary nodules (IPNs). False positive results occur, especially from active granulomatous nodules. A PET-based imaging agent with superior specificity to 18F-FDG for IPNs, is badly needed, especially in areas of endemic granulomatous nodules. Somatostatin receptors (SSTR) are expressed in many malignant cells including small cell and non-small cell lung cancers (NSCLCs). 68Ga-DOTATATE, a positron emitter labeled somatostatin analog, combined with PET/CT imaging, may improve the diagnosis of IPNs over 18F-FDG by reducing false positives. Our study purpose was to test this hypothesis in our region with high endemic granulomatous IPNs.MethodsWe prospectively performed 68Ga-DOTATATE PET/CT and 18F-FDG PET/CT scans in the same 30 patients with newly diagnosed, treatment-naïve lung cancer (N = 14) or IPNs (N = 15) and one metastatic nodule. 68Ga-DOTATATE SUVmax levels at or above 1.5 were considered likely malignant. We analyzed the scan results, correlating with ultimate diagnosis via biopsy or 2-year chest CT follow-up. We also correlated 68Ga-DOTATATE uptake with immunohistochemical (IHC) staining for SSTR subtype 2A (SSTR2A) in pathological specimens.ResultsWe analyzed 31 lesions in 30 individuals, with 14 (45%) being non-neuroendocrine lung cancers and 1 (3%) being metastatic disease. McNemar's result comparing the two radiopharmaceuticals (p = 0.65) indicates that their accuracy of diagnosis in this indication are equivalent. 68Ga-DOTATATE was more specific (94% compared to 81%) and less sensitive 73% compared to 93%) than 18F-FDG. 68Ga-DOTATATE uptake correlated with SSTR2A expression in tumor stroma determined by immunohistochemical (IHC) staining in 5 of 9 (55%) NSCLCs.Conclusion68Ga-DOTATATE and 18F-FDG PET/CT had equivalent accuracy in the diagnosis of non-neuroendocrine lung cancer and 68Ga-DOTATATE was more specific than 18F-FDG for the diagnosis of IPNs. IHC staining for SSTR2A receptor expression correlated with tumor stroma but not tumor cells.
| S-EPMC5300187 | biostudies-literature
Project description:PurposeComputed tomography is the standard method by which pulmonary nodules are detected. Greater than 40% of pulmonary biopsies are not lung cancer and therefore not necessary, suggesting that improved diagnostic tools are needed. The LungLB™ blood test was developed to aid the clinical assessment of indeterminate nodules suspicious for lung cancer. LungLB™ identifies circulating genetically abnormal cells (CGACs) that are present early in lung cancer pathogenesis.MethodsLungLB™ is a 4-color fluorescence in-situ hybridization assay for detecting CGACs from peripheral blood. A prospective correlational study was performed on 151 participants scheduled for a pulmonary nodule biopsy. Mann-Whitney, Fisher's Exact and Chi-Square tests were used to assess participant demographics and correlation of LungLB™ with biopsy results, and sensitivity and specificity were also evaluated.ResultsParticipants from Mount Sinai Hospital (n = 83) and MD Anderson (n = 68), scheduled for a pulmonary biopsy were enrolled to have a LungLB™ test. Additional clinical variables including smoking history, previous cancer, lesion size, and nodule appearance were also collected. LungLB™ achieved 77% sensitivity and 72% specificity with an AUC of 0.78 for predicting lung cancer in the associated needle biopsy. Multivariate analysis found that clinical and radiological factors commonly used in malignancy prediction models did not impact the test performance. High test performance was observed across all participant characteristics, including clinical categories where other tests perform poorly (Mayo Clinic Model, AUC = 0.52).ConclusionEarly clinical performance of the LungLB™ test supports a role in the discrimination of benign from malignant pulmonary nodules. Extended studies are underway.
| S-EPMC10240808 | biostudies-literature