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1038 Loss of PD-1 signals improves CD8+ TIL function in a cell intrinsic and cell extrinsic manner
  1. Samuel Markson1,
  2. Kristen Pauken1,
  3. Vikram Juneja1,
  4. Osmaan Shahid2,
  5. Kelly Burke1,
  6. Jared Rowe1,
  7. Jacklyn Long1,
  8. Megan Fung1,
  9. Jacob Luber2,
  10. Jennifer Judge1,
  11. Alison Ringel1,
  12. Marcia Haigis1,
  13. Meromit Singer2 and
  14. Arlene Sharpe1
  1. 1Harvard Medical School, Boston, MA, USA
  2. 2Dana-Farber Cancer Institute, Boston, MA, USA


Background Blockade of PD-1 or its ligand PD-L1 has led to improved clinical outcomes in diverse cancer types, and has been approved by the FDA for use in over 20 different advanced stage cancers. Though PD-1 pathway inhibitors show great promise, the mechanisms contributing to protective anti-tumor immunity following loss of PD-1 signaling remain incompletely understood.

Methods To elucidate the cell intrinsic consequences of PD-1 loss, as well as the impact of this loss on neighboring PD-1-expressing cells, we developed an inducible PD-1 knockout (KO) model whereby PD-1 could be deleted on roughly half of the CD8+ T cell population.

Results Using paired single cell RNA seq and TCR seq, we found that PD-1-expressing CD8+ T cells in the tumor received much of the same therapeutic benefit as those T cells lacking PD-1. Thus, many of the anti-tumoral changes that occurred in the CD8+ TIL population were not dependent on a cell intrinsic loss of PD-1, but instead were shared between cells that do or do not express PD-1.

Conclusions These data suggest that PD-1 inhibitors can act beyond each individual cell that they contact to promote a heightened anti-tumor state, and can impact T cell functions independent of direct PD-1 blockade.

Acknowledgements This work was supported by NIH P50 CA101942 and P01 AI56299.

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