Immunostimulation with chemotherapy in the era of immune checkpoint inhibitors
Abstract
Conventional chemotherapeutics have been developed into clinically useful agents based on their ability to preferentially kill malignant cells, generally owing to their elevated proliferation rate. Nonetheless, the clinical activity of various chemotherapies is now known to involve the stimulation of anticancer immunity either by initiating the release of immunostimulatory molecules from dying cancer cells or by mediating off-target effects on immune cell populations. Understanding the precise immunological mechanisms that underlie the efficacy of chemotherapy has the potential not only to enable the identification of superior biomarkers of response but also to accelerate the development of synergistic combination regimens that enhance the clinical effectiveness of immune checkpoint inhibitors (ICIs) relative to their effectiveness as monotherapies. Indeed, accumulating evidence supports the clinical value of combining appropriately dosed chemotherapies with ICIs. In this Review, we discuss preclinical and clinical data on the immunostimulatory effects of conventional chemotherapeutics in the context of ICI-based immunotherapy.
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Immunogenic cell death is featured with upregulated DAMPs such as secretion of IFN-I, exposure of CRT on the cell membrane, leak of ATP, and release of HMGB1.
“Immunogenic cell death is featured with some upregulated damage-associated molecular patterns (DAMPs) such as the secretion of IFN-I, the exposure of endoplasmic reticulum proteins especially calreticulin (CRT, an eat-me signal) on cell membrane, the leak of ATP (a find-me signal), and the release of high-mobility group box 1 (HMGB1) [35].”
From Combination strategies with PD-1/PD-L1 blockade: current advances and future directions (2022) · cites this paper as [35]
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Self-citation
- Authors
- Galluzzi, L., Humeau, J., Buqué, A., Zitvogel, L., & Kroemer, G.
- Affiliations
- Université Paris Cité (FR)
- Université Paris-Sud (FR)
- Weill Cornell Medicine (US)
- Karolinska University Hospital (SE)
- Corresponding author
- Galluzzi, Lorenzo
- Kroemer, Guido
- Venue
- Nature Reviews Clinical Oncology
- Published
- 2020-08-05
- Volume
- 17
- Issue
- 12
- Pages
- 725-741
- ISSN
- 1759-4774 (ISSN-L)
- 1759-4782
- OpenAlex
- W3047618013
- Cited by
- 1,349
- References
- 281
- Citations by year
- 2026: 150 · 2025: 232 · 2024: 269 · 2023: 282 · 2022: 272 · 2021: 127 · 2020: 17
- FWCI
- 18.73
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Nature Reviews Clinical Oncology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Agence Nationale de la Recherche (ANR-16-ECVD-0008)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Ferroptosis and cancer prognosis
- Keywords
- chemotherapy, immune checkpoint inhibitors, immunostimulation, cancer immunotherapy, combination therapy, immunogenic cell death, synergy mechanism, treatment response biomarkers
- MeSH terms
- Antineoplastic Agents, Immunological, Immune Checkpoint Inhibitors, Humans, Immunity, Immunization, Immunotherapy, Neoplasms
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