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Updated: Jul 6, 2026
In Vivo Immunogenicity Screening of Tumor-Derived Extracellular Vesicles by Flow Cytometry of Splenic T Cells
Published on: September 23, 2021
Capitalizing on the immunogenicity of dying tumor cells
1Department of Medical Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Abstract:
Cancer cell death occurs continually during tumor development and progression, whereas the selective killing of surviving cancer cells remains the primary objective of antineoplastic treatments. Recent insights into the immunologic consequences of cancer cell death have begun to elucidate the ways in which host antitumor immunity is shaped during cancer pathogenesis and then modulated by therapeutic intervention. Dying tumor cells evoke a range of host responses, dependent in part upon the mode of cell death, which may either impede or foster additional immune-mediated cancer destruction. Within the tumor microenvironment, the capture of apoptotic tumor cells by macrophages and dendritic cells may trigger tolerance networks that contribute to immune suppression, whereas the uptake of necrotic cancer cells may engender inflammatory pathways that fuel antitumor cytotoxicity. Milk fat globule epidermal growth factor 8, a phosphatidylserine-binding protein, and MHC class I chain-related protein A, an NKG2D ligand, play key roles in these competing outcomes. A deeper understanding of the mechanisms underlying the immunogenicity of dying cells informs the crafting of strategies that exploit endogenous or treatment-induced cancer cell death as the basis for stimulating sustained host antitumor cytotoxic reactions.
Insights
Cancer cell death influences antitumor immunity. The way tumor cells die—apoptosis or necrosis—determines if the immune response is suppressed or activated, impacting cancer treatment effectiveness.
Area of Science:
- Immunology
- Oncology
- Cell Biology
Background:
- Cancer cell death is a continuous process during tumor development.
- Selective killing of cancer cells is the main goal of cancer treatments.
- The immunologic consequences of cancer cell death shape host antitumor immunity.
Purpose of the Study:
- To elucidate how host antitumor immunity is shaped by cancer cell death during pathogenesis.
- To understand how therapeutic interventions modulate immune responses to dying cancer cells.
- To explore the mechanisms by which dying tumor cells influence immune-mediated cancer destruction.
Main Methods:
- Analysis of host responses to different modes of cancer cell death (apoptosis vs. necrosis).
- Investigation of the roles of milk fat globule epidermal growth factor 8 and MHC class I chain-related protein A.
- Examination of immune cell interactions (macrophages, dendritic cells) with dying tumor cells within the tumor microenvironment.
Main Results:
- Apoptotic tumor cell uptake by immune cells can induce immune tolerance and suppression.
- Necrotic cancer cell uptake can trigger inflammatory pathways that enhance antitumor cytotoxicity.
- Specific molecules like MFG-E8 and MIC A play critical roles in determining these immune outcomes.
Conclusions:
- The mode of cancer cell death significantly impacts the host's immune response, with implications for cancer treatment.
- Understanding these mechanisms is crucial for developing strategies that leverage cancer cell death to stimulate anti-tumor immunity.
- Targeting pathways involved in the immunogenicity of dying cells can enhance the efficacy of cancer therapies.
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