scholarly journals Activation of T Cells upon Treatment with Bispecific Antibodies Correlates with the Expression of Co-Inhibitory Receptors on Tumor-Infiltrating Lymphocytes in Human Lung Cancer

2014 ◽  
Vol 25 ◽  
pp. vi1
Author(s):  
D. Thommen ◽  
J. Schreiner ◽  
P. Herzig ◽  
P. Mueller ◽  
V. Karanikas ◽  
...  
2017 ◽  
Vol 40 (1) ◽  
pp. 1-10 ◽  
Author(s):  
Si Yuan Sheng ◽  
Yong Gu ◽  
Chuan Gang Lu ◽  
Ying Ying Tang ◽  
Jian Yong Zou ◽  
...  

1989 ◽  
Vol 43 (4) ◽  
pp. 619-623 ◽  
Author(s):  
Tokujiro Yano ◽  
Kosei Yasumoto ◽  
Masatoshi Togami ◽  
Teruyoshi Ishida ◽  
Genki Kimura ◽  
...  

2020 ◽  
Vol 10 ◽  
Author(s):  
Yongyuan Chen ◽  
Zhongwei Xin ◽  
Lijian Huang ◽  
Lufeng Zhao ◽  
Shijie Wang ◽  
...  

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A71-A71
Author(s):  
Yukari Kobayashi ◽  
Koji Nagaoka ◽  
Kaori Kubo ◽  
Toshikazu Nishie ◽  
Sachiko Okamoto ◽  
...  

BackgroundT-cells that target tumor neoantigens arising from cancer mutations are the primary mediators of cancer immunotherapies. Identifying neoantigens and T-cells that recognize them is essential for T-cell-based immunotherapy. However, neoantigen-reactive Tumor-infiltrating lymphocytes (TILs) are highly differentiated or exhausted with a limited proliferative capacity; it is challenging to expand them for a sufficient number to probe their specificity. Therefore, we developed a novel cloning and expression system to examine TCRs discovered by single-cell sequencing of TILs for their neoantigen-specificity.MethodsTILs of lung cancer and sarcoma were analyzed. Surgically removed tumors were divided into several pieces. They were enzymatically digested to prepare fresh tumor digest (FTD) and cryopreserved. They were used to generate TIL cultures and perform WES and RNA-Seq to identify tumor-specific mutations. MHCflurry was used to predict the binding affinity of potential epitopes arising from these mutations to HLA class I. Peptides that were predicted to bind to patients‘ own MHC class I molecules strongly were then synthesized. Single TILs isolated with the ICELL8® cx system (Takara Bio) were dispensed into a nanowell TCR chip containing preprinted barcodes. Barcoded cDNAs were PCR-amplified in-chip, pooled off-chip, and used as a template in the TCR-specific PCR or for the whole transcriptome library generation of 5’ ends of all transcripts. Based on single-cell transcriptome data and TCR profiles of TILs, we predict and prioritize neoantigen-specific TCRs and cloned them into siTCR® retrovirus vectors. These TCRs were transduced into SUP-T1-based reporter cells in which ZsGreen fluorescent protein expression is controlled by AP-1 and NFAT binding sites. TCR-expressing reporter cells were cocultured with patient autologous APCs pulsed with a pool of candidate neoantigen peptides. ZsGreen expression indicates that TCRs match their cognate neoantigens.ResultsIn a lung cancer patient, we set up 18 TIL cultures and obtained 12 TILs. TILs were cocultured with FTD; IFN-γ production was measured by ELISA to evaluate their reactivity to the autologous tumor. NGS identified 197 somatic mutations, 4 fusion genes, and 8 highly expressed cancer-testis antigens. Among them, 339 candidate peptides were synthesized and screened. In addition, we cloned 3 pairs of TCRαβ chains from most expanded TIL cultures and 4 TCRs from ex vivo TILs with exhausted phenotype. Two reporter cells that express TCRs from exhausted TILs responded to the same neoantigen peptide.ConclusionsGenerating TCR expressing cell lines facilitated the identifying neoantigens and their cognate TCR sequences from patients.Ethics ApprovalG3545


Genes ◽  
2021 ◽  
Vol 12 (9) ◽  
pp. 1458
Author(s):  
Ya-Sian Chang ◽  
Ming-Hung Hsu ◽  
Siang-Jyun Tu ◽  
Ju-Chen Yen ◽  
Ya-Ting Lee ◽  
...  

This study was designed to characterize the microbiomes of the lung tissues of lung cancer patients. RNA-sequencing was performed on lung tumor samples from 49 patients with lung cancer. Metatranscriptomics data were analyzed using SAMSA2 and Kraken2 software. 16S rRNA sequencing was also performed. The heterogeneous cellular landscape and immune repertoires of the lung samples were examined using xCell and TRUST4, respectively. We found that nine bacteria were significantly enriched in the lung tissues of cancer patients, and associated with reduced overall survival (OS). We also found that subjects with mutations in the epidermal growth factor receptor gene were less likely to experience the presence of Pseudomonas. aeruginosa. We found that the presence of CD8+ T-cells, CD4+ naive T-cells, dendritic cells, and CD4+ central memory T cells were associated with a good prognosis, while the presence of pro B-cells was associated with a poor prognosis. Furthermore, high clone numbers were associated with a high ImmuneScore for all immune receptor repertoires. Clone numbers and diversity were significantly higher in unpresented subjects compared to presented subjects. Our results provide insight into the microbiota of human lung cancer, and how its composition is linked to the tumor immune microenvironment, immune receptor repertoires, and OS.


2017 ◽  
Vol 12 (11) ◽  
pp. S2013
Author(s):  
Y.K. Chae ◽  
W. Choi ◽  
W. Bae ◽  
J. Anker ◽  
A. Davis ◽  
...  

2018 ◽  
Author(s):  
Nhan Tu ◽  
Thu Le Trinh ◽  
Sarah S. Donatelli ◽  
Melba M. Tejera ◽  
Danielle L. Gilvary ◽  
...  

2015 ◽  
Vol 37 (4) ◽  
pp. 1560-1571 ◽  
Author(s):  
Yiting Geng ◽  
Yingjie Shao ◽  
Wenting He ◽  
Wenwei Hu ◽  
Yanjie Xu ◽  
...  

Background/Aims: The role of Tumor-infiltrating lymphocytes (TILs) in the prognosis of patients with lung cancer is still controversial. We performed a meta-analysis to evaluate the prognostic role of TILs in lung cancer. Methods: Studies were recruited by searching PubMed, Embase and the Cochrane Library and assessed by further quality evaluation. The pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated to investigate the association between TIL subsets and lung cancer patients' outcome. Results: A total of 29 articles including 8,600 patients were enrolled into the meta-analysis. Our results indicated that high level of CD8+ cells infiltration in tumor stroma (TS) or tumor nest (TN) was associated with better OS in lung cancer patients (HR = 0.76, 95% CI 0.62-0.93, P = 0.006; HR = 0.80, 95% CI 0.67-0.96; P = 0.018, respectively). Similar results could be also observed in CD3+ T cells infiltration. High CD4+ T lymphocytes infiltration in TS was explicitly accompanied by better OS (HR = 0.65, 95% CI 0.46-0.91; P = 0.013), rather than in TN. In contrast, high density of FOXP3+ T cells infiltration in TS showed a poor PFS (HR = 2.67, 95% CI, 1.74-4.08, P < 0.001). Conclusion: This meta-analysis clarified that high level of CD8+ and CD3+ T cells infiltration in TS or TN, and high CD4+ T lymphocytes infiltration in TS showed better OS in lung cancer patients, whereas high density of FOXP3+ T cells infiltration in TS could be recognized as a negative prognostic factor.


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