scholarly journals Characterization of Distinct T Cell Receptor Repertoires in Tumor and Distant Non-tumor Tissues from Lung Cancer Patients

2019 ◽  
Vol 17 (3) ◽  
pp. 287-296 ◽  
Author(s):  
Xiang Wang ◽  
Botao Zhang ◽  
Yikun Yang ◽  
Jiawei Zhu ◽  
Shujun Cheng ◽  
...  
Keyword(s):  
Lung Cancer ◽  
T Cell ◽  
Cancer Patients ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Lung Cancer Patients ◽  
Tumor Tissues

Comprehensive analysis of T-cell receptor sequencing in resectable squamous cell lung cancer patients with neoadjuvant therapy of PD-1 inhibitor and chemotherapy.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e21012-e21012
Author(s):  
Yuan Feng ◽  
Shanshan Xiao ◽  
Wei Sun ◽  
Yuanyuan Ma ◽  
Yang Hong ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Lymph Nodes ◽  
Cancer Patients ◽  
Squamous Cell ◽  
Cell Receptor ◽  
Lung Cancer Patients ◽  
Cell Clones ◽  
Tumor Tissues ◽  
Patient Groups

e21012 Background: Cancer therapies alter the tumor microenvironment such as the infiltration of T cells. Neoadjuvant therapy to squamous cell lung cancer patients using PD-1 inhibitor expands specific T cell clones. However, the T cell clones and diversity in tumors and lymph nodes according to different neoadjuvant settings remain largely unknown. In this study, we used T-cell receptor (TCR) sequencing technology to investigate the TCR clonotypes and diversities in squamous cell NSCLC patients who received neoadjuvant chemotherapy and PD-1 inhibitor plus chemotherapy. Methods: Tumor tissues, non-metastatic lymph nodes (NMLN)s, and available metastatic lymph nodes (MLNs) were collected from two patient groups. Each group enrolled three patients who received either neoadjuvant chemotherapy or PD-1 inhibitor plus chemotherapy. DNA samples were harvested and processed for multiplex PCR for the third complementary determining region (CDR3) of TCR-β chain followed by the next generation sequencing analysis. Differences of the CDR3 clonotypes and clonal diversities were analyzed by bioinformatics tools including the Mixcr software. Results: For all the six patients, TCR clonotypes in the tumor tissues were found to be fewer than those from the lymph nodes in the same patient, consistent with a hypothesis that most of the tumor infiltrated T cells after therapy derive from the lymph nodes. Some clonotypes among the top 10 highest frequencies were found in different samples from the same patient, further supporting the lymph node origin of the tumor infiltrating T cells after therapies. Interestingly, TCR clonal diversity was higher in the NMLNs compared with the MLNs, but clonotype overlap with tumor tissues was higher in the MLNs than NMLNs; these results could imply that TCR clonotypes in the primary lymph node were more stimulated. Additionally, there were very few clonotypes shared between different patients, indicating the heterogeneity of immune response for different individuals. Due to the limited sample size, we could not find the systemic difference between the two patient groups. Conclusions: TCR sequencing technology can detect the CDR3 clonotypes in tumor tissues and lymph nodes of cancer patients, providing new opportunities for revealing patients' response to chemotherapy and immunotherapy. Further analysis will be performed to investigate TCR clonotype differences caused by immunotherapy.

Characteristics of T-cell receptor repertoire between lung cancer patients and healthy people.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e20728-e20728 ◽  
Author(s):  
Naixin Liang ◽  
Si Chen ◽  
Yuting Yi ◽  
Yan-Fang Guan ◽  
Xuefeng Xia ◽  
...  
Keyword(s):  
Lung Cancer ◽  
T Cell ◽  
Cancer Patients ◽  
Peripheral Blood ◽  
Cell Receptor ◽  
Shannon Index ◽  
Shannon’S Entropy ◽  
Lung Cancer Patients ◽  
Shannon's Entropy ◽  
Tcr Repertoire

e20728 Background: Deep sequencing studies on T cell receptor (TCR) repertoire have provided a wealth of information, such as immune status, virus infection history and so on. As we all known, the thymus begins to involute at the time of birth, so does the immune system. We can use TCR sequence to describe changes in human’s immune system with age, the difference between males and females and immune stat of cancers. Methods: We analyzed TCRβrepertoire in 334 healthy individuals without cancer, aged 2–83 years, and 207 lung cancers. In detail, genomic DNA was extracted from peripheral blood and used to amplified and sequenced the CDR3 region of rearranged TCRβ genes. Finally, we got the relative frequencies of individual T cell clones. Shannon’s entropy was calculated on the clonal abundance of all productive TCR sequences. The normalized Shannon’s entropy (Shannon index) was determined by dividing Shannon’s entropy by the natural logarithm of the number of unique productive TCR sequences. HEC was defined by a CDR3 aa clonotype clonal frequency exceeding 0.1%. Results: Analysis had been made to test the age relationship among a cluster of commonly used immune parameters, such as Shannon’s entropy, clonality and so on. Two outcomes, Shannon index and HEC, had showed a more closed correlation with age. Shannon indexs were significantly decreasing with age (p = 6.2×10-11), while HECs increased with age (p = 5.3×10-10) . Comparison of the peripheral blood T cell repertoire diversity between male and female, we found TCRβdiversity decreases more rapidly in 20 to 40 years for males than for females. No gender difference was observed in the youngest cohort and the oldest age cohort. Lung cancer patients has a lower T cell diversity compared with health people aged 40 years or more (6.43±1.30 vs 6.71±1.70, p = 6.3×10-5). Conclusions: Our data suggest that the human peripheral blood TCR repertoire diversity decrease from young ( < 20 years) to middle-aged ( 20 to 65 years ) to elderly adults ( > 65 years). Moreover, TCR repertoire displays significant gender difference in the 20-40 years age group. Lung cancer patients suffer a poorer immune state than healthy people.

Abstract 4159: Characterization of the T-cell receptor (TCR) repertoire in extensive disease small cell lung cancer (ED SCLC)

2016 ◽  
Author(s):  
Maen Hussein ◽  
Sharon Wilks ◽  
Marc Monte ◽  
Donald A. Richards ◽  
Jerome H. Goldschmidt ◽  
...  
Keyword(s):  
Lung Cancer ◽  
T Cell ◽  
Small Cell Lung Cancer ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Small Cell ◽  
Small Cell Lung ◽  
Extensive Disease ◽  
Tcr Repertoire

scholarly journals Characterization of human T cells reactive with the Mycoplasma arthritidis-derived superantigen (MAM): generation of a monoclonal antibody against V beta 17, the T cell receptor gene product expressed by a large fraction of MAM-reactive human T cells.

1991 ◽  
Vol 174 (4) ◽  
pp. 891-900 ◽  
Author(s):  
S M Friedman ◽  
M K Crow ◽  
J R Tumang ◽  
M Tumang ◽  
Y Q Xu ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Cell Activity ◽  
Cell Receptor ◽  
Cytotoxic T Cell ◽  
Mycoplasma Arthritidis ◽  
Human T Cells

While all known microbial superantigens are mitogenic for human peripheral blood lymphocytes (PBL), the functional response induced by Mycoplasma arthritidis-derived superantigen (MAM) is unique in that MAM stimulation of PBL consistently results in T cell-dependent B cell activation characterized by polyclonal IgM and IgG production. These immunostimulatory effects of MAM on the humoral arm of the human immune system warranted a more precise characterization of MAM-reactive human T cells. Using an uncloned MAM reactive human T cell line as immunogen, we have generated a monoclonal antibody (mAb) (termed C1) specific for the T cell receptor V beta gene expressed by the major fraction of MAM-reactive human T cells, V beta 17. In addition, a V beta 17- MAM-reactive T cell population exists, assessed by MAM, induced T cell proliferation and cytotoxic T cell activity. mAb C1 will be useful in characterizing the functional properties of V beta 17+ T cells and their potential role in autoimmune disease.

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