Immune Escape

Tumor cells can escape the antitumor immune response in several ways

Tumor cells can evade the immune system by disrupting any of the key T-cell activities necessary to initiate and perpetuate an antitumor immune response: T-cell generation, T-cell infiltration, or tumor cell killing.1-3

Disruption of any steps of the cancer immunity cycle can ultimately result in tumor growth.1

T-cell activities essential to cancer immunity cycle

*Tumor cell killing by CD8+ T cells.

PD-L1 may need to be targeted simultaneously with other pathways to restore the cancer immunity cycle

As a key immunosuppressive driver, the PD-L1 pathway is an important target that can help invigorate antitumor T-cell activity in the tumor microenvironment.3,4

  • PD-L1 inhibition can help restore tumor cell killing4
    • In cancer, the PD-L1 ligand is expressed on tumor cells and immune cells
    • When bound to its receptors, PD-1 and B7.1 on T cells, PD-L1 deactivates cytotoxic T cells
    • PD-L1 inhibition prevents T-cell deactivation, which can reinvigorate antitumor T-cell activity and lead to tumor cell killing
PD-L1 inhibition preventing T-cell deactivation

MHC=major histocompatibility complex; TCR=T-cell receptor.

However, cancers may use multiple immune escape mechanisms. Targeting PD-L1 simultaneously with other pathways may be necessary to restore a fully functional cancer immunity cycle.3

Genentech is actively researching pathway combinations with PD-L1.5-7

Combination strategies to restore cancer immunity

PD-L1=programmed death-ligand 1; VEGF=vascular endothelial growth factor.

References

  1. Chen DS, Mellman I. Immunity. 2013;39:1-10. PMID: 23890059
  2. Chen DS, Mellman I. Nature. 2017;541:321-330. PMID: 28102259
  3. Kim JM, Chen DS. Ann Oncol. 2016;27:1492-1504. PMID: 27207108
  4. Chen DS, Irving BA, Hodi FS. Clin Cancer Res. 2012;18:6580-6587. PMID: 23087408
  5. US National Institutes of Health. ClinicalTrials.gov. https://www.clinicaltrials.gov/ct2/show/NCT02788279. Accessed November 1, 2017.
  6. US National Institutes of Health. ClinicalTrials.gov. https://www.clinicaltrials.gov/ct2/show/NCT02420821. Accessed November 1, 2017.
  7. US National Institutes of Health. ClinicalTrials.gov. https://www.clinicaltrials.gov/ct2/show/NCT02425891. Accessed November 1, 2017.
  8. Gebremeskel S, Johnston B. Oncotarget. 2015;6:41600-41619. PMID: 26486085