Persistence and enrichment of dominant T cell clonotypes in expanded tumor-infiltrating lymphocytes of breast cancer

Background Adoptive cell therapy using tumor-infiltrating lymphocytes (TILs) has shown promising results in cancer treatment, including breast cancer. However, clonal dynamics and clinical significance of TIL expansion ex vivo remain poorly understood. Methods We investigated T cell receptor (TCR) r...

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Published in:British journal of cancer 2024-07, Vol.131 (1), p.196-204
Main Authors: Ham, Baknoon, Kim, Su Yeon, Kim, Young-Ae, Han, DoYeon, Park, Taehyun, Cha, Sumin, Jung, SungWook, Kim, Jong Hyeok, Park, Gisung, Gong, Gyungyub, Lee, Hee Jin, Shin, Junyoung
Format: Article
Language:English
Subjects:
631/250/251
631/67/580
Biomedical and Life Sciences
Biomedicine
Breast cancer
Cancer Research
Cancer therapies
CD4 antigen
CD8 antigen
Cell culture
Cell therapy
Complementarity-determining region 3
Drug Resistance
Epidemiology
Lymphocytes T
Molecular Medicine
Oncology
Peripheral blood
T cell receptors
Tumor-infiltrating lymphocytes
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Summary:Background Adoptive cell therapy using tumor-infiltrating lymphocytes (TILs) has shown promising results in cancer treatment, including breast cancer. However, clonal dynamics and clinical significance of TIL expansion ex vivo remain poorly understood. Methods We investigated T cell receptor (TCR) repertoire changes in expanded TILs from 19 patients with breast cancer. We compared TCR repertoire of TILs at different stages of expansion, including initial (2W TILs) and rapid expansion (REP TILs), and their overlap with formalin fixed paraffin embedded (FFPE) and peripheral blood. Additionally, we examined differences in TCR repertoire between CD4+ and CD8+ REP TILs. Results In descending order of proportion, average of 60% of the top 10% clonotypes of FFPE was retained in 2W TIL (60% in TRB, 64.7% in TRA). Among the overlapped clonotypes between 2W TILs and REP TILs, 69.9% was placed in top 30% of 2W TIL. The proportion of clonotypes in 2W TIL and REP TIL showed a significant positive correlation. CD4+ and CD8+ T cells show similar results in diversity and CDR3 length. Conclusions Our study traces the changes in TILs repertoire from FFPE to 2W TIL and REP TIL and confirmed that clonotypes with high frequencies in TILs have a high likelihood of maintaining their priority throughout culture process.
ISSN:0007-0920
1532-1827
1532-1827
DOI:10.1038/s41416-024-02707-6