PD-L1 Inhibition + Antigen Release

Tumor antigen release is a critical step in initiating the cancer immunity cycle

The cancer immunity cycle can be initiated when tumor antigens from dying tumor cells are released and are captured by dendritic cells (DCs) to activate CD8+ T cells.1

Tumors may escape the immune response by disrupting the generation of active T cells in various ways1,2:

  • Tumors with low mutation burden release fewer diverse antigens that may result in poor tumor immunogenicity
  • Tumors can inhibit the maturation of DCs, which are needed to activate cytotoxic T cells

Chemotherapy-induced cell death can help initiate the antitumor immune response

Certain classes of chemotherapy may help initiate the cancer immunity cycle by increasing tumor antigen release and stimulating DC maturation, leading to T-cell activation.3,4

Chemotherapy-induced antigen release leading to T-cell activation

Combining this effect with PD-L1 inhibition may help perpetuate the antitumor immune response

The release of tumor antigens can ultimately result in activated T cells reaching the tumor microenvironment. PD-L1 inhibition may help maintain this effect by preventing T-cell deactivation, leading to T cells attacking the tumor and the release of additional tumor antigens.1,3,5,6

Genentech is researching the synergistic potential of increasing antigen release and targeting PD-L1 in various tumor types.7,8

PD-L1 inhibition + antigen release restores cancer immunity

PD-L1=programmed death-ligand 1.

References

  1. Chen DS, Mellman I. Immunity. 2013;39:1-10. PMID: 23890059
  2. Kim JM, Chen DS. Ann Oncol. 2016;27:1492-1504. PMID: 27207108
  3. Gebremeskel S, Johnston B. Oncotarget. 2015;6:41600-41619. PMID: 26486085
  4. Galluzzi L, Buqué A, Kepp O, Zitvogel L, Kroemer G. Nat Rev Immunol. 2017;17:97-111. PMID: 27748397
  5. Chen DS, Mellman I. Nature. 2017;541:321-330. PMID: 28102259
  6. Swart M, Verbrugge I, Beltman JB. Front Oncol. 2016;6:233. PMID: 27847783
  7. US National Institutes of Health. ClinicalTrials.gov. https://www.clinicaltrials.gov/ct2/show/NCT02425891. Accessed November 1, 2017.
  8. US National Institutes of Health. ClinicalTrials.gov. https://www.clinicaltrials.gov/ct2/show/NCT02367794. Accessed November 1, 2017.
  9. Kroemer G, Galluzzi L, Kepp O, Zitvogel L. Annu Rev Immunol. 2013;31:51-72. PMID: 23157435