Abstract | BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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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Authors | Heejae Lee, Young-Ae Kim, Youngho Kim, Hye Seon Park, Jeong-Han Seo, Hyun Lee, Gyungyub Gong, Hee Jin Lee |
Journal | Cancer immunology, immunotherapy : CII
(Cancer Immunol Immunother)
Vol. 69
Issue 11
Pg. 2381-2391
(Nov 2020)
ISSN: 1432-0851 [Electronic] Germany |
PMID | 32529292
(Publication Type: Journal Article)
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Chemical References |
- Antineoplastic Agents
- PDCD1 protein, human
- Programmed Cell Death 1 Receptor
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Topics |
- Adult
- Aged
- Aged, 80 and over
- Antineoplastic Agents
(therapeutic use)
- Chemotherapy, Adjuvant
(methods)
- Female
- Humans
- Lymphocytes, Tumor-Infiltrating
(immunology)
- Middle Aged
- Neoadjuvant Therapy
(methods)
- Programmed Cell Death 1 Receptor
(drug effects, metabolism)
- Triple Negative Breast Neoplasms
(drug therapy, immunology, pathology)
- Tumor Cells, Cultured
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