Explore Chemotherapy-Induced Cell Death

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  • Overview
  • Initiating Chemotherapy-Induced Cell Death
  • Potentials of Combinations
Overview

Chemotherapy-induced cell death can play an important role in eliciting immune responses

The antitumour immune response can be characterised by a series of stepwise events known as the cancer immunity cycle. The first steps in this process involve neoantigen release by dying cancer cells and subsequent neoantigen capture by dendritic cells (DCs).1

cancer immunity cycle
 
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Initiating Chemotherapy-Induced Cell Death

Chemotherapy elicits immunostimulatory effects and promotes antitumour activity

Chemotherapy-induced cell death promotes recruitment of DCs to the site of cell death and tumour antigen presentation to T cells, generating a robust, antigen-specific immune response.2-4

cancer antigen presentation

Additionally, chemotherapy induces immunostimulatory effects that may promote antitumour activity, such as decreasing the number of myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs) with immunosuppressive function.5

immune cells
decrease tregs
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Potentials of Combinations

Chemotherapy may synergise with PD-L1 inhibition

Chemotherapy-induced cell death can initiate the cancer immunity cycle and sensitise tumours to immune checkpoint inhibition. Targeting PD-L1 can help maintain this effect by countering immunosuppressive activity in the tumour microenvironment, which leads to tumour cell killing and the release of additional tumour antigens. Accordingly, approaches that utilise chemotherapy and PD-L1 in combination may enhance the antitumour response, as demonstrated in preclinical data.6-9

chemotherapy and PD-L1

 

Roche is investigating the synergistic potential of chemotherapy and PD-L1 pathway inhibition in cancer types such as lung cancer and breast cancer

 
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References 
  1. Chen DS, Mellman I. Oncology meets immunology: the cancer-immunity cycle. Immunity. 2013;39:1-10. PMID: 23890059
  2. Pol J, Vacchelli E, Aranda F, et al. Trial Watch: Immunogenic cell death inducers for anticancer chemotherapy. Oncoimmunology. 2015;4:e1008866. PMID: 26137404
  3. Garg AD, Dudek-Peric AM, Romano E, and Agostinis P. Immunogenic cell death. Int J Dev Biol. 2016;59:131-140. PMID: 26374534
  4. Galluzzi L, Buque A, Kepp O, Zitvogel L, Kroemer G. Immunogenic cell death in cancer and infectious disease. Nat Rev Immuno. 2017;17:97-111. PMID: 27748397
  5. Chen G, Emens L. Chemoimmunotherapy: reengineering tumor immunity. Cancer Immunol Immunother. 2013;62(2):203-216. PMID: 23389507
  6. Chen DS, Irving BA, Hodi FS. Molecular pathways: next-generation immunotherapy—inhibiting programmed death-ligand 1 and programmed death-1. Clin Cancer Res. 2012;18(24):6580-6587. PMID: 23087408
  7. Chen DS, Mellman I. Elements of cancer immunity and the cancer-immune set point. Nature. 2017;541:321-330. PMID: 28102259
  8. Kim JM, Chen DS. Immune escape to PD-L1/PD-1 blockade: seven steps to success (or failure). Annals of Oncology. 2016;27:1492-1504. PMID: 27207108
  9. Swart M, Verbrugge I, Beltman JB. Combination approaches with immune-checkpoint blockade in cancer therapy. Front Oncol. 2016;6:233. doi:10.3389/fonc.2016.00233. PMID: 27847783

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