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Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research

5877 - TCR beta chain convergence defines the tumor infiltrating T cell repertoire of melanoma and non-small cell lung carcinoma.

Date

20 Oct 2018

Session

Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research

Presenters

Timothy Looney

Citation

Annals of Oncology (2018) 29 (suppl_8): viii14-viii57. 10.1093/annonc/mdy269

Authors

T. Looney1, G. Lowman1, L. Miller1, E. Linch2

Author affiliations

  • 1 Clinical Next-generation Sequencing Division, Thermo Fisher Scientific, 94080 - South San Francisco/US
  • 2 Clinical Next-generation Sequencing Division, Thermo Fisher Scientific, 94080 - Carlsbad/US
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Resources

Abstract 5877

Background

T cell convergence refers to the process whereby antigen-driven selection enriches for T cell receptors having a shared antigen specificity but different amino acid or nucleotide sequence. T cell recruitment and expansion within the tumor microenvironment (TME) may be directed by responses to tumor neoantigen, suggesting that elevated T cell convergence could be a general feature of the tumor infiltrating T cell repertoire. Here we evaluate evidence for T cell convergence in tumor biopsy from research subjects with melanoma and non-small cell lung carcinoma (NSCLC) and peripheral blood leukocytes (PBL) from healthy donors.

Methods

Total RNA from 63 melanoma and 19 NSCLC tumor biopsy research samples (non-FFPE) was extracted for use in long-amplicon TCRB chain sequencing (mean amplicon of 330bp covering CDR1, 2 and 3) via the Oncomine TCR Beta-LR Research Assay. To evaluate T cell convergence, we searched for instances where TCRB chains were identical in amino acid space but had distinct nucleotide sequences owing to N-addition and exonucleotide chewback within the V-D and D-J junctions of the CDR3. To provide context, we evaluated evidence for T cell convergence in PBL T cell repertoires derived from 16 healthy donors.

Results

Sequencing of melanoma biopsy research samples typically yielded within the range of 2000 to 8000 clones per sample. Convergent T cell receptors were identified in the great majority of melanoma and NSCLC tumor infiltrating T cell repertoires having greater than 100 detected clones (92% and 100%, respectively). The frequency of convergent T cell rearrangements was significantly greater in melanoma and NSCLC tumor biopsies than T cell repertoires derived from healthy PBL research samples.

Conclusions

These data suggest that T cell convergence may be a common feature of the melanoma and NSCLC infiltrating T cell repertoire. Convergence was more frequently observed within the TME than T cell repertoires derived from healthy PBL, consistent with elevated antigen-driven T cell selection within the TME. The finding of elevated T cell convergence in melanoma and NSCLC suggests that convergence may be a hallmark of immunogenic tumors. For research use only.

Clinical trial identification

Legal entity responsible for the study

Thermo Fisher Scientific.

Funding

Thermo Fisher Scientific.

Editorial Acknowledgement

Disclosure

T. Looney, G. Lowman, L. Miller, E. Linch: Employee: Thermo Fisher Scientific.

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