Checkpoint and Vaccine Translation: T Cell Mechanism and Biomarkers

Characterize patient response to Anti-PD-1 and Anti-CTLA-4 therapies through IsoCode profiling of tumor-infiltrating T cells.

IsoCode Data

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) 

Publications

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.

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