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T cell receptor repertoires of ex vivo–expanded tumor-infiltrating lymphocytes from breast cancer patients

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Abstract

A higher level of tumor-infiltrating lymphocytes (TILs) is associated with better prognosis in breast cancer patients. Adoptive transfer of lymphocytes coupled with conventional therapies has appealed to many clinicians and investigators as an effective treatment strategy for cancer patients, which necessitates efficient activation and expansion of cytotoxic T lymphocytes precisely targeting cancer cells. To comprehensively understand composition of TILs and to provide a grounding in adoptive T cell therapy, we analyzed the T cell receptor (TCR) repertoires in ex vivo–expanded TILs from nine breast cancer patients via next-generation sequencing. For the three of them, TCR repertoires of TILs gathered after the initial culture during 2 weeks were additionally analyzed and compared to those of TILs that underwent ex vivo rapid expansion procedure (REP). Diversity of TCR repertoire was variable among the patients. V/J segment usage in the clonotypes was similar among patients, with variable distribution of read counts for each V/J segment. The top 50% of most frequently observed VJ combinations was present in > 80% of the total clonotypes. Compared with TCGA data, the samples contained a similar amount of recurrent CDR3 sequences, but clonotype expansion was variable among the samples. In terms of clinicopathologic factor, presence of in vitro reactivity among triple-negative breast cancer cases seemed to be related to lower Shannon’s index, but p value was not statistically significant. In addition, the proportion of CD45RO+ cells out of CD8+ T cells were negatively correlated with Shannon’s diversity index for both TCRα and TCRβ chains (p = 0.010) via Spearman test. In this study, we identified a heterogeneous pattern of expanded T cell clones and stable usage of V/J segments in ex vivo–expanded TILs from breast cancer patients. Further large-scale studies are requisite to elucidate the clinical significance of TCR repertoires.

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Author notes

  1. In Ah Park and Hajar Rajaei contributed equally to this work.

Authors and Affiliations

  1. Department of Pathology and Tranlational Genomics, Samsung Medical Center, Seoul, 06351, Republic of Korea

    In Ah Park

  2. Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, Republic of Korea

    Hajar Rajaei, Young-Ae Kim, Hyeonjin Lee, Heejae Lee, Jeong-Han Seo, Sun-Hee Heo, Gyungyub Gong & Hee Jin Lee

  3. Asan Center for Cancer Genome Discovery, Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, Republic of Korea

    Young-Ae Kim, Hyeonjin Lee, Heejae Lee, Jeong-Han Seo & Sun-Hee Heo

  4. Department of Pathology, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, 06591, Republic of Korea

    In Hye Song

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Précis

· Despite of intricate heterogeneity of T cell receptor clonotypes, usage of V/J segments in ex vivo–expanded tumor-infiltrating lymphocytes from breast cancer patients is stable.

· Diversity of T cell receptor clonotypes seems to be decreased during ex vivo rapid expansion protocol.

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Park, I.A., Rajaei, H., Kim, YA. et al. T cell receptor repertoires of ex vivo–expanded tumor-infiltrating lymphocytes from breast cancer patients. Immunol Res 68, 233–245 (2020). https://doi.org/10.1007/s12026-020-09150-8

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