Exposure to anti-PD-1 causes functional differences in tumor-infiltrating lymphocytes in rare solid tumors.
Eur J Immunol
; 49(12): 2245-2251, 2019 12.
Article
en En
| MEDLINE
| ID: mdl-31532833
ABSTRACT
The pervasive use of therapeutic antibodies targeting programmed cell death protein 1 (PD-1) to boost anti-tumor immunity has positioned this approach to become the standard-of-care for some solid tumor malignancies. However, little is known as to how blockade of PD-1 may alter the function or phenotype of tumor-infiltrating lymphocytes (TIL). We used our ongoing Phase II clinical trial of pembrolizumab for patients with rare solid tumors from various types (NCT02721732) with matched core biopsies taken at baseline and after initial dose of anti-PD-1 (15-21 days post-dose) to elucidate this question. One fresh core needle biopsy was used to propagate TIL ex vivo to analyze phenotype and function using flow cytometry in both CD8+ and CD4+ TIL populations. An enriched CTLA-4 expression in the CD4+ TIL population was observed in TIL expanded from the on-treatment samples compared to TIL expanded from the matched baseline (n = 22, p = 0.0007) but was not observed in patients who experienced tumor regression. Impact on functionality was evaluated by measuring secretion of 65 soluble factors by expanded TIL from 26 patients at baseline and on-treatment. The CD8+ TIL population demonstrated a diminished cytokine secretion profile post-pembrolizumab. Overall, our study assesses the ramifications of one dose of anti-PD-1 on TIL in rare solid tumor types.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Linfocitos T CD4-Positivos
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Linfocitos Infiltrantes de Tumor
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Linfocitos T CD8-positivos
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Enfermedades Raras
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Anticuerpos Monoclonales Humanizados
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Antígeno B7-H1
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Proteínas de Neoplasias
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Neoplasias
Tipo de estudio:
Etiology_studies
Límite:
Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Eur J Immunol
Año:
2019
Tipo del documento:
Article