Immunogenic cell death and immunogenic surrender: related but distinct mechanisms of immune surveillance

Our plain-English summary of Immunogenic cell death and immunogenic surrender: related but distinct mechanisms of immune surveillance, by R. Mezzapelle, M.E. Bianchi, M.P. Crippa (Cell Death & Disease, 2021).

The study

• Authors: R. Mezzapelle, M.E. Bianchi, M.P. Crippa
• Journal: Cell Death & Disease
• Published: 2021;12(10):869
• Cited by: 12 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

In plain English

This was a short commentary. The authors compared two ways the immune system may recognize cancer cells: immunogenic cell death, and immunogenic surrender, which they had described earlier. They also reported new experiments in male BALB/c mice injected in the abdomen (peritoneum) with mouse malignant mesothelioma cells (AB1 cells). Asbestos was not part of the study. Mice given fully reduced HMGB1 (one form of the protein) three times a week had tumor growth similar to untreated mice and no significant difference in survival (p = 0.64). In laboratory dishes, fully reduced HMGB1 did not lower the CD47 protein on the mesothelioma cell surface, and at 0.1 nM it made the cells grow faster. Mice given an antibody that blocks HMGB1 did not fare worse than control mice. Mice given the antibody together with BoxA, a fragment of HMGB1, still showed a treatment effect. The authors concluded that the two mechanisms differ, and that extracellular HMGB1 is needed for immunogenic cell death but not for immunogenic surrender. The article did not state how many mice were in each group.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Commentary (comment article) presenting new mouse and cell-culture experiments
• Who was studied: Male BALB/c mice aged 6 to 8 weeks, injected into the peritoneum with AB1 mouse malignant mesothelioma cells. AB1 mesothelioma cells were also grown in culture. Numbers of mice were not stated.
• Exposure: No asbestos exposure was studied. The mice received one of the following: fully reduced HMGB1 (50 μg, three times a week); an anti-HMGB1 neutralizing antibody (clone DPH1.1, 200 μg, once a week); BoxA (800 μg, three times a week); both the antibody and BoxA; or PBS as a control.
• Main results:
  • Mesothelioma-bearing mice treated with fully reduced HMGB1 showed no significant difference in survival compared with untreated mice (p = 0.64).
  • Fully reduced HMGB1 did not reduce surface CD47 on AB1 mesothelioma cells at any dose tested.
  • Adding 0.1 nM fully reduced HMGB1 to cultured mesothelioma cells made them grow faster than untreated cells.
  • Mice receiving the anti-HMGB1 antibody alone did not fare worse than control mice.
  • Mice given the anti-HMGB1 antibody together with BoxA still showed a therapeutic effect.
• The authors' conclusion: The authors concluded that immunogenic cell death and immunogenic surrender differ in at least two respects. First, in immunogenic surrender the cells do not die on their own. Second, extracellular HMGB1 is needed for immunogenic cell death but not for immunogenic surrender.
• Limitations the authors state:
  • The authors did not test whether the XBP1 and ATF6 branches of the unfolded protein response are necessary for immunogenic surrender.
  • The authors said further work is needed to find out whether HPVs and HTLV-1 activate immunogenic surrender.

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• Ecteinascidin synthetic analogues: a new class of selective inhibitors of transcription, exerting immunogenic cell death in refractory malignant pleural mesothelioma — I.C. Salaroglio, P. Aviles, et al. (2024)
• Potential of fluoropyrimidine to be an immunologically optimal partner of immune checkpoint inhibitors through inducing immunogenic cell death for thoracic malignancies — H. Kozai, H. Ogino, et al. (2024)
• Autophagy facilitates the release of immunogenic signals following chemotherapy in 3D models of mesothelioma — C. Follo, Y. Cheng, et al. (2019)
• Mechanism of Collaborative Enhancement of Binding of Paired Antibodies to Distinct Epitopes of Platelet Endothelial Cell Adhesion Molecule-1 — R. Kiseleva, C.F. Greineder, et al. (2017)
• Human malignant mesothelioma is recapitulated in immunocompetent BALB/c mice injected with murine AB cells — R. Mezzapelle, E. Rrapaj, et al. (2016)

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