PD-1 blockade inhibits hematogenous spread of poorly immunogenic tumor cells by enhanced recruitment of effector T cells
Abstract
Since metastasis is the major cause of death for cancer patients, there is an urgent need to develop new therapies to control hematogenous dissemination of cancer cells. Previously we and others demonstrated a novel mechanism that allows tumors to escape from the host immune response by expressing PD-L1 which can negatively regulate immune response through the interaction with PD-1, an immunoinhibitory receptor belonging to the CD28 family. In this study, we report that hematogenous spread of poorly immunogenic B16 melanoma cells to the liver was inhibited in PD-1-deficient mice. After inoculation to spleen, PD-L1 was induced on tumor cells, which did not express PD-L1 in vitro. As compared with wild-type mice, intrasplenic injection of B16 cells into PD-1-deficient mice showed enhanced induction of effector T cells in spleen, prolonged T cell proliferation and cytokine production, and augmented homing of effector T cells to tumor sites in the liver, resulting in accumulation of effector T cells in the tumor sites. PD-1 blockade by genetic manipulation or antibody treatment inhibited not only hematogenous dissemination of B16 melanoma cells to the liver on the C57BL/6 background, but also dissemination of CT26 colon cancer cells to the lung on the BALB/c background. These results suggest that PD-1 blockade may be a powerful tool for treatment of hematogenous spread of various tumor cells.
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Overcoming checkpoints through therapeutic antibodies targeting CTLA-4, PD-1, or PD-L1 promotes anti-tumor T cell responses in mice and cancer patients.
“Overcoming such checkpoints through the use of therapeutic antibodies targeting the CTLA-4, PD-1, or PD-L1 cell-surface receptors was shown to be instrumental in promoting anti-tumor T cell responses in mice and in cancer patients”
From LXR/ApoE Activation Restricts Innate Immune Suppression in Cancer (2018) · cites this paper as Iwai et al., 2005
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- Authors
- Iwai, Y.
- Affiliations
- Kyoto University (JP)
- Corresponding author
- Iwai, Y.
- ORCID
- Iwai, Y.
- Venue
- International Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2004-12-20
- Volume
- 17
- Issue
- 2
- Pages
- 133-144
- ISSN
- 0953-8178 (ISSN-L)
- 1460-2377
- OpenAlex
- W2107408397
- Cited by
- 527
- References
- 6
- Citations by year
- 2026: 16 · 2025: 27 · 2024: 42 · 2023: 35 · 2022: 31 · 2021: 42 · 2020: 35 · 2019: 39 · 2018: 30 · 2017: 24 · 2016: 33 · 2015: 42 · 2014: 16 · 2013: 17 · 2012: 14
- FWCI
- 5.61
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- International Immunology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- anti-PD-1 therapy, PD-L1, tumor immunogenicity, hematogenous metastasis, B16 melanoma, CT26 cells, T cell homing, tumor immune evasion, liver metastasis, lung metastasis, T cell proliferation
- MeSH terms
- Animals, Antigens, Surface, Colonic Neoplasms, Liver, Liver Neoplasms, Lung Neoplasms, Lymphocyte Activation, Melanoma, Experimental, Mice, Transgenic, T-Lymphocytes, Cytotoxic, Cytokines, Tumor Escape, Apoptosis Regulatory Proteins, Mice, Programmed Cell Death 1 Receptor
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