Work

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

Year: 2018

Type: article

Abstract: 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. Legal entity responsible for the study: Thermo Fisher Scientific. Funding: Thermo Fisher Scientific. Disclosure: T. Looney, G. Lowman, L. Miller, E. Linch: Employee: Thermo Fisher Scientific.

Source: Annals of Oncology

DOI: 10.1093/annonc/mdy269.064

Authors: T. Looney, G. Lowman, L. Miller, E. Linch

Institution: Thermo Fisher Scientific (United States)

Language: English

Topic: Cancer Immunotherapy and Biomarkers

Subfield: Oncology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $5,080