Single-cell cytokine profiling of tumor-infiltrating T cells to measure patient responses to anti-PD-1 therapy
| العنوان: | Single-cell cytokine profiling of tumor-infiltrating T cells to measure patient responses to anti-PD-1 therapy |
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| المؤلفون: | Sean Mackay, Jing Zhou, Antonella Bacchiocchi, Kevin Morse, Ruth Halaban, Brianna Flynn, Rong Fan, Patrick Paczkowski |
| المصدر: | Journal of Clinical Oncology. 35:49-49 |
| بيانات النشر: | American Society of Clinical Oncology (ASCO), 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | 0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, business.industry, Cell, Anti pd 1, Cancer, medicine.disease, Cytokine profiling, 03 medical and health sciences, 030104 developmental biology, medicine.anatomical_structure, Internal medicine, Medicine, business |
| الوصف: | 49 Background: Functional alteration of tumor-infiltrating T lymphocytes (TILs) may serve as a predictor for clinical outcome in cancer patients receiving immunotherapy.To evaluate TILs function unleashed by anti-PD-1 blocking, we employed a single-cell technology integrated with automated bioinformatics to simultaneously measure 17 cytokines secreted by single TILs, permitting the full spectrum delineation of anti-tumor T cell functions in patients with metastatic melanoma. Methods: TILs were enriched from biopsied melanoma tissues digested with enzymes, stimulated with anti-CD3 at 37°C, 5% CO2 for 24 hrs and loaded into a single-cell barcode chip (SCBC) containing ~12000 microchambers. Each chamber (~1.2 nl) was pre-patterned with a complete copy of a 17-plex antibody array. Cells on the SCBC were imaged and incubated for 16 hrs at 37°C, 5% CO2; single-cell cytokine signals were captured with a microarray scanner. The polyfunctional expression (2+ cytokines per cell) of single TILs was evaluated across 4 groups: Effector (Granzyme B, IFN-γ, MIP-1α, Perforin, TNF-α), Stimulatory (GM-CSF, IL-2, IL-5, IL-8, IL-9), Regulatory (IL-4, IL-10, IL-13, IL-22), and Inflammatory (IL-6, IL-17A, MCP-1). Results: Single-cell TILs analysis revealed significant increase of polyfunctional cytokines in patients who responded to anti-PD-1 therapy, compared to those resistant to therapy or in the control group. It was further revealed that the major contributions to enhanced polyfunctional strength are dominated by effector and stimulatory cytokines – both associated with anti-tumor immunity. Notably, TILs of patients responding to therapy exhibited polyfunctional secretions containing a subset of cells co-secreting Granzyme B, IFN- γ, MIP-1 α, and IL-8, which upon further validation is potentially a biomarker to predict clinical outcome of melanoma patients treated by checkpoint immunotherapy. Conclusions: Single-cell multiplexed cytokine profiling is capable of dissecting the full spectrum of immune functions associated with anti-tumor T cell immunity and more accurately measuring the function of TILs for predicting the response of patients receiving anti-PD-1 blocking therapy. |
| تدمد: | 1527-7755 0732-183X |
| DOI: | 10.1200/jco.2017.35.7_suppl.49 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::05a650e043634008b4c2d6329a29e098 https://doi.org/10.1200/jco.2017.35.7_suppl.49 |
| رقم الانضمام: | edsair.doi...........05a650e043634008b4c2d6329a29e098 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15277755 0732183X |
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| DOI: | 10.1200/jco.2017.35.7_suppl.49 |