scholarly journals Tumor‐infiltrating CD8 + T cell is prognostic and predicts adjuvant chemotherapy benefit in patients with limited‐stage small cell esophageal carcinoma

2021 ◽  
Vol 11 (6) ◽  
Author(s):  
Zhihui Zhang ◽  
Chaoqi Zhang ◽  
Guochao Zhang ◽  
Yuejun Luo ◽  
Liyan Xue ◽  
...  
Keyword(s):  
T Cell ◽  
Adjuvant Chemotherapy ◽  
Esophageal Carcinoma ◽  
Cd8 T Cell ◽  
Small Cell ◽  
Limited Stage

scholarly journals m6A regulator expression profile predicts the prognosis, benefit of adjuvant chemotherapy, and response to anti-PD-1 immunotherapy in patients with small-cell lung cancer

BMC Medicine ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Zhihui Zhang ◽  
Chaoqi Zhang ◽  
Yuejun Luo ◽  
Peng Wu ◽  
Guochao Zhang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
T Cell ◽  
Adjuvant Chemotherapy ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Cd8 T Cell ◽  
Small Cell ◽  
Clinicopathological Parameters ◽  
Small Cell Lung ◽  
Platinum Based Chemotherapy

Abstract Background Small cell lung cancer (SCLC) is lethal and possesses limited therapeutic options. Platinum-based chemotherapy—with or without immune checkpoint inhibitors (anti-PDs)—is the current first-line therapy for SCLCs; however, its associated outcomes are heterogeneous. N6-methyladenosine (m6A) is a novel and decisive factor in tumour progression, chemotherapy resistance, and immunotherapy response. However, m6A modification in SCLC remains poorly understood. Methods We systematically explored the molecular features and clinical significance of m6A regulators in SCLC. We then constructed an m6A regulator-based prognostic signature (m6A score) based on our examination of 256 cases with limited-stage SCLC (LS-SCLC) from three different cohorts—including an independent cohort that contained 150 cases with qPCR data. We additionally evaluated the relationships between the m6A score and adjuvant chemotherapy (ACT) benefits and the patients’ responses to anti-PD-1 treatment. Immunohistochemical (IHC) staining and the HALO digital pathological platform were used to calculate CD8+ T cell density. Results We observed abnormal somatic mutations and expressions of m6A regulators. Using the LASSO Cox model, a five-regulator-based (G3BP1, METTL5, ALKBH5, IGF2BP3, and RBM15B) m6A score was generated from the significant regulators to classify patients into high- and low-score groups. In the training cohort, patients with high scores had shorter overall survival (HR, 5.19; 2.75–9.77; P < 0.001). The prognostic accuracy of the m6A score was well validated in two independent cohorts (HR 4.6, P = 0.006 and HR 3.07, P < 0.001). Time-dependent ROC and C-index analyses found the m6A score to possess superior predictive power than other clinicopathological parameters. A multicentre multivariate analysis revealed the m6A score to be an independent prognostic indicator. Additionally, patients with low scores received a greater survival benefit from ACT, exhibited more CD8+ T cell infiltration, and were more responsive to cancer immunotherapy. Conclusions Our results, for the first time, affirm the significance of m6A regulators in LS-SCLC. Our multicentre analysis found that the m6A score was a reliable prognostic tool for guiding chemotherapy and immunotherapy selections for patients with SCLC.

scholarly journals NFATc1 promotes anti-tumoral effector functions and memory CD8+ T cell differentiation during non-small cell lung cancer development

2018 ◽  
pp. canres.3297.2017 ◽  
Author(s):  
Lisanne Heim ◽  
Juliane Friedrich ◽  
Marina Engelhardt ◽  
Denis I Trufa ◽  
Carol I. Geppert ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Differentiation ◽  
T Cell ◽  
Small Cell Lung Cancer ◽  
Cd8 T Cell ◽  
Small Cell ◽  
T Cell Differentiation ◽  
Cancer Development ◽  
Small Cell Lung ◽  
Effector Functions

O-152 Immunotherapy with gene-modified allogenic cells successfully induced CD8 T cell and clinical responses in patients with advanced non-small cell lung cancer (NSCLC)

Lung Cancer ◽  
2003 ◽  
Vol 41 ◽  
pp. S46-S47
Author(s):  
Luis E. Raez ◽  
Peter A. Cassileth ◽  
James Schlesselman ◽  
Swaminathan Padmanabhan ◽  
Eva Fisher ◽  
...  
Keyword(s):  
Lung Cancer ◽  
T Cell ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Cd8 T Cell ◽  
Small Cell ◽  
Small Cell Lung ◽  
Clinical Responses

Radiotherapy and chemotherapy are associated with improved outcomes over surgery and chemotherapy in the management of limited-stage small cell esophageal carcinoma

2013 ◽  
Vol 106 (3) ◽  
pp. 317-322 ◽  
Author(s):  
Mao-Bin Meng ◽  
Nicholas G. Zaorsky ◽  
Chao Jiang ◽  
Li-Jun Tian ◽  
Huan-Huan Wang ◽  
...  
Keyword(s):  
Esophageal Carcinoma ◽  
Small Cell ◽  
Limited Stage ◽  
Improved Outcomes

scholarly journals Induction of CD8 T-cell-Ifn-γ response and positive clinical outcome after immunization with gene-modified allogeneic tumor cells in advanced non-small-cell lung carcinoma

2003 ◽  
Vol 10 (11) ◽  
pp. 850-858 ◽  
Author(s):  
Luis E Raez ◽  
Peter A Cassileth ◽  
James J Schlesselman ◽  
Swaminathan Padmanabhan ◽  
Eva Z Fisher ◽  
...  
Keyword(s):  
T Cell ◽  
Clinical Outcome ◽  
Tumor Cells ◽  
Lung Carcinoma ◽  
Small Cell Lung Carcinoma ◽  
Cd8 T Cell ◽  
Small Cell ◽  
Small Cell Lung ◽  
Cell Lung Carcinoma ◽  
Ifn Γ

scholarly journals Multimodality therapy is recommended for limited-stage combined small cell esophageal carcinoma

2015 ◽  
pp. 437 ◽  
Author(s):  
Mao-Bin Meng ◽  
Huan-Huan Wang ◽  
Nicholas Zaorsky ◽  
Chao Jiang ◽  
Zhi-Qiang Wu ◽  
...  
Keyword(s):  
Esophageal Carcinoma ◽  
Small Cell ◽  
Multimodality Therapy ◽  
Limited Stage

Trial in progress: Neoadjuvant immune checkpoint blockade in resectable malignant pleural mesothelioma.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. TPS9078-TPS9078
Author(s):  
Joshua E. Reuss ◽  
Boris Sepesi ◽  
Christian Diego Rolfo ◽  
Marianna Zahurak ◽  
Valsamo Anagnostou ◽  
...  
Keyword(s):  
T Cell ◽  
Adjuvant Chemotherapy ◽  
Malignant Pleural Mesothelioma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
Stage I ◽  
Stopping Rules ◽  
Pleural Mesothelioma ◽  
Limited Stage

TPS9078 Background: While the role of surgery in limited-stage (stage I-III) malignant pleural mesothelioma (MPM) is controversial, many centers have adopted an aggressive tri-modality approach incorporating (neo)adjuvant chemotherapy, surgical resection and radiotherapy. Despite this, most patients relapse and die from their disease. Immune checkpoint blockade (ICB) has shown promise in advanced MPM, but the mechanisms of response and resistance remain elusive. Improving the mechanistic understanding of ICB in MPM while concurrently optimizing the treatment strategy for limited-stage MPM are two urgent unmet needs. This multicenter multi-arm phase I/II study seeks to evaluate the safety and feasibility of neoadjuvant ICB in resectable MPM, incorporating novel genomic and immunologic analyses to deliver mechanistic insight into the biology of ICB in MPM. Methods: Patients with surgically resectable stage I-III treatment-naïve epithelioid or biphasic MPM receive neoadjuvant treatment with nivolumab every 2 weeks for 3 doses with or without 1 dose of ipilimumab (arm A: nivolumab monotherapy; arm B: nivolumab + ipilimumab). After macroscopic complete resection, patients receive optional investigator-choice adjuvant chemotherapy +/- radiation. Following this, patients will receive up to 1 year of adjuvant nivolumab. Feasibility and safety are co-primary endpoints of this study with feasibility defined by a delay in surgery of ≤24 days from the preplanned surgical date and safety defined by adverse events according to CTCAE v5.0. Bayesian-designed stopping rules have been implemented for feasibility and safety. Secondary endpoints include assessment of pathologic response and radiographic response using RECIST 1.1 for MPM. Correlative analyses will be performed on tissue specimens obtained pre- and post-ICB, as well as blood obtained pre, during, and post-ICB. Key correlates include multiplex immunofluorescence and longitudinal ctDNA assessment. Whole exome sequencing, T-cell receptor sequencing, and the MANAFEST functional neoantigen assay will be utilized to identify neoantigen-specific T-cell clonotypes and track these clonotypes temporally (during/post ICB) and spatially (across immune compartments). Single-cell RNA sequencing will be used to characterize the functionality of expanded T-cell clonotypes. Accrual to arm B will commence following complete accrual to arm A with a planned total enrollment of 30 patients. This study is open with 1 patient enrolled at the time of submission. Clinical trial information: NCT03918252.

Lack of CD8 + T cell effector differentiation during priming mediates checkpoint blockade resistance in non–small cell lung cancer

2021 ◽  
Vol 6 (64) ◽  
Author(s):  
Brendan L. Horton ◽  
Duncan M. Morgan ◽  
Noor Momin ◽  
Maria Zagorulya ◽  
Elen Torres-Mejia ◽  
...  
Keyword(s):  
Lung Cancer ◽  
T Cell ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Cd8 T Cell ◽  
Small Cell ◽  
Checkpoint Blockade ◽  
Small Cell Lung ◽  
Cell Effector
Sign in / Sign up

Export Citation Format

Share Document