The clinical significance of adoptive tumor-infiltrating lymphocyte (TIL) therapy has been demonstrated in many clinical trials. We analyzed the in vitro reactivity of cultured TILs against autologous breast cancer cells.
TILs and cancer cells were cultured from 31 breast tumor tissues. Reactivity of TILs against cancer cells was determined by measuring secreted interferon-gamma. Expression levels of epithelial markers, major histocompatibility complex molecules, and programmed death-ligand 1 (PD-L1) in cancer cells, and T cell markers (memory, T cell activation and exhaustion, and regulatory T cell markers) in expanded TILs were analyzed and compared between the reactive and non-reactive groups.
In seven cases, TILs showed reactivity to autologous cancer cells. Six of these cases were associated with triple-negative breast cancer (TNBC). All reactive TNBCs were derived from surgical specimens after neoadjuvant chemotherapy (NAC). Higher expression of Ki67 in tumor tissues and lower expression of PD-L1 in cultured cancer cells were associated with reactivity. Proliferation of reactive TILs was high. High proportions of T cells and PD-1+CD4+ and PD1+CD8+ T cells were associated with reactivity in TNBC cases, while other activation or exhaustion markers were not.
TILs from approximately half the TNBC cases with NAC showed reactivity against autologous cancer cells. The proportion of PD-1+ T cells was higher in the reactive group. Adoptive TIL therapy combined with PD-1 inhibitors might be promising for TNBC patients with residual tumors after NAC.
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The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
Adoptive cell transfer
Epithelial cell adhesion molecule
- HER2+ :
Human epidermal growth factor receptor 2-positive
Myeloid-derived suppressor cells
Major histocompatibility complex
Natural killer T
Peripheral blood mononuclear cell
T cell receptor
Tertiary lymphoid structure
Triple-negative breast cancer
Regulatory T cell
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This study was supported by the Korean Health Technology R&D Project, Ministry of Health & Welfare (HI15C0708 and HI17C0337) and the Asan Institute for Life Sciences, Asan Medical Center, Seoul, Korea (2018IL0169, 2019IL0169, and 2019IL0839).
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The authors declare that they have no competing interests.
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Tumor tissues were obtained from patients along with their consent to the use of the specimen for research purposes. This study was approved by the Institutional Review Board of Asan Medical Center (IRB#2015-0438).
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Lee, H., Kim, Y., Kim, Y. et al. Clinicopathological factors associated with tumor-infiltrating lymphocyte reactivity in breast cancer. Cancer Immunol Immunother (2020). https://doi.org/10.1007/s00262-020-02633-5
- Tumor-infiltrating lymphocytes
- Breast cancer
- Adoptive cell therapy