Checkpoint Mechanism Biomarker Discovery
Isoplexis’ single cell profiling of tumor-infiltrating T-cells has shown the potential to characterize patient response to Anti-PD-1 therapy for biomarker development. The heterogeneity and small sample size of TILs in primary tumor tissues from patients with metastatic melanoma necessitate single-cell highly-multiplexed analysis for precise yet comprehensive evaluation of TILs function kinetics. IsoPlexis' IsoCode platform integrated with IsoSpeak's automated bioinformatics platform is capable of providing a full spectrum delineation of single TILs’ cytokine profile unleashed by anti-PD-1 blocking.
Figure 1: Polyfunctional overview of analyzed CD8+ TILs samples, showing samples from responders have 2x more polyfunctional cells than untreated samples, and 5x higher polyfunctional strength. (Zhou 2017)
Figure 2: CD8+ TILs single-cell secretion intensities of each cytokine. The percentage of cells strongly secreting at least one cytokine in responding patients’ samples is five times higher (21.2%) than in nonresponding patients’ samples (3.8%), and twice as high as in untreated patients’ samples (10.5%). (Zhou 2017)
Mackay S, Flynn B, Morse K, Paczkowski P, Bacchiocchi A, Heath JR, Fan R, Halaban R, and Zhou J. Single-Cell Cytokine Profiling of Tumor-Infiltrating T Cells to Measure Patient Responses to Anti-PD-1 Therapy. Presented at TRCCC Annual Meeting 2018.
Mackay S, Flynn B, Morse K, Paczkowski P, Bacchiocchi A, Fan R, Halaban R, and Zhou J. Single-Cell Cytokine Profiling of Tumor-Infiltrating T Cells to Measure Patient Responses to Anti-PD-1 Therapy. Journal of Clinical Oncology, 35 (9), Suppl. 7S (2017).
Lu Y, Xue Q, Eisele MR, Sulistijo E, Brower K, Han L, Amir ED, Pe’er D, Miller-Jensen K, and Fan R. Highly Multiplexed Profiling of Immune Effector Functions Reveals Deep Functional Heterogeneity in Response to Pathogenic Ligands. Proc. Natl. Acad. Sci., 112 (7), 607-615 (2015).
Lu Y, Chen JJ, Mu L, Xue Q, Wu Y, Wu PH, Li J, Vortmeyer AO, Miller-Jensen K, Wirtz D, and Fan R. High-throughput Secretomic Analysis of Single Cells to Assess Functional Cellular Heterogeneity. Analytical Chemistry, 85 (4), 2548– 2556 (2013).
Ma C, Fan R, Ahmad H, Shi Q, Comin-Anduix B, Chodon T, Koya RC, Liu CC, Kwong GA, Radu CG, Ribas A, and Heath JR. A Clinical Microchip for Evaluation of Single Immune Cells Reveals High Functional Heterogeneity in Phenotypically Similar T Cells. Nature Medicine, 17, 738-743 (2011).
Local Dream Team Develops Cancer Treatment That's Saving Lives. A dream team of Caltech and UCLA scientists and doctors have created a treatment that's giving hope to cancer patients who once had none. The medication was developed by chemistry professor James Heath and his lab at Caltech in Pasadena, who work day and night, to help UCLA oncologist Antoni Ribas try to cure his incurable cancer patients.