Exploring the pathways underlying cancer immune evasion

Tumours can inhibit the antitumour immune response by disrupting the balance governing the steps of the cancer immunity cycle through multiple mechanisms. The goal of cancer immunotherapy research is to understand these mechanisms to counteract the tumour's ability to suppress the immune response. These pathways may include1,2

  • Stimulatory factors that promote the immune response against cancer
  • Inhibitory factors that keep the cycle in check to prevent autoimmunity

Explore the PD-L1 Pathway (Programmed Death-Ligand 1)

Stimulatory And Inhibitory Factors Involved In The Cancer Immunity Cycle1,3

the cancer immunity cycle

Stimulatory Factors

Inhibitors

*Focus of research by Roche.

STEP 1: Release of cancer cell antigens

  • Immunogenic cell death
  • Tolergenic cell death

STEP 2: CANCER ANTIGEN PRESENTATION

  • TNFα
  • IL-1
  • IFNα
  • CD40L/CD40*
  • CDN
  • ATP
  • HMGB1
  • TLR
  • IL-10
  • IL-4
  • IL-13

STEP 3: PRIMING AND ACTIVATION

  • CD28/B7.1
  • CD137/CD137L
  • OX40/OX40L*
  • CD27/CD70*
  • HVEM
  • GITR
  • IL-2*
  • IL-12
  • CTLA4/B7.1
  • PD-L1/B7.1*
  • PD-L1/PD-1*
  • Prostaglandins

STEP 4: TRAFFICKING OF T CELLS TO TUMORS

  • CX3CL1
  • CXCL9
  • CXCL10
  • CCL5

STEP 5: INFILTRATION OF T CELLS INTO TUMORS

  • LFA1/ICAM1
  • Selectins
  • VEGF*
  • Endothelin B receptor

STEP 6: RECOGNITION OF CANCER CELLS BY T CELLS

  • T-cell receptor*
  • Reduced pMHC on cancer cells

STEP 7: KILLING OF CANCER CELLS

  • IFNγ
  • T-cell granule content
  • PD-L1/B7.1*
  • PD-L1/PD-1*
  • IDO*
  • TGFβ
  • BTLA
  • TIM-3/phospholipids
  • LAG-3
  • Arginase
  • MICA-MICB
  • B7-H4
  • VISTA

ATP=adenosine triphosphate; BTLA=B- and T-lymphocyte attenuator; CDN=cyclic dinucleotide; CSF-1R=colony-stimulating factor 1; CTLA4=cytotoxic T-lymphocyte antigen-4; CXCL/CCL=chemokine motif ligands; GITR=glucocorticoid-induced TNFR family-related gene; HMGB1=high-mobility group protein B1; HVEM=herpes virus entry mediator; ICAM1=intracellular adhesion molecule 1; IDO=indoleamine 2,3-dioxygenase; IFN=interferon; IL=interleukin; LAG-3=lymphocyte-activation gene 3 protein; LFA1=lymphocyte function-associated antigen-1; MIC=MHC class I polypeptide-related sequence protein; PD-L1=programmed death-ligand 1; TGF=transforming growth factor; TIM-3=T cell immunoglobulin domain and mucin domain-3; TLR=toll-like receptor; TNF=tumour necrosis factor; VEGF=vascular endothelial growth factor; VISTA=V-domain Ig suppressor of T cell activation.