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PD-1 Blockade Expands Intratumoral Memory T Cells
Antoni Ribas1, Daniel Sanghoon Shin2, Jesse Zaretsky2
1Division of Hematology-Oncology, Department of Medicine, University of California Los Angeles, Los Angeles, California. Division of Surgical-Oncology, Department of Surgery, University of California Los Angeles, Los Angeles, California. Department of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, California. Jonsson Comprehensive Cancer Center, Los Angeles, California. bcomin@mednet.ucla.edu aribas@mednet.ucla.edu.
Programmed cell death protein 1 (PD-1) blockade therapy increases T cells, B cells, and myeloid-derived suppressor cells within tumors. Responders showed expanded CD8(+) effector memory T cells, crucial for anti-tumor immunity.
Area of Science:
- Immunology
- Oncology
- Cell Biology
Background:
- Programmed cell death protein 1 (PD-1) blockade therapy is a key cancer treatment.
- T cells are critical mediators of anti-tumor responses to PD-1 blockade.
- Understanding cellular changes within tumors during PD-1 blockade is essential for optimizing treatment.
Purpose of the Study:
- To characterize leukocyte phenotypes in tumor biopsies from patients receiving PD-1 blockade therapy.
- To identify cellular changes associated with response versus non-response to pembrolizumab.
- To investigate the role of specific T cell subsets in PD-1 blockade efficacy.
Main Methods:
- Analysis of 102 tumor biopsies from 53 patients treated with pembrolizumab.
- Single-cell dissociation and multicolor flow cytometry.
- Computational approaches to resolve leukocyte phenotypes and quantify cell frequencies.
Main Results:
- A significant increase in T cells was observed in therapy responders.
- Intratumoral B cells and monocytic myeloid-derived suppressor cells increased during treatment.
- CD8(+) effector memory T cells showed the most prominent intratumoral expansion in responders.
- CD4(+) effector T cells increased in nonresponding tumors, while CD4(+) effector memory T cells decreased.
Conclusions:
- PD-1 blockade therapy alters the tumor immune microenvironment by increasing T cells, B cells, and myeloid-derived suppressor cells.
- Expansion of CD8(+) effector memory T cells is a hallmark of response to PD-1 blockade.
- Distinct T cell dynamics in responders and non-responders may inform future therapeutic strategies.
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