cancer immunotherapy: immune checkpoint · 2018-04-10 · blocking key immune checkpoint inhibitors...

abcam.com/cancer

Cancer immunotherapy: immune checkpoint

T cell proliferation

T cell activation

T cell priming

Tumor infiltrationAntigen capture

Dendritic cell

Activated T cell

Tumor T cell

Tumor apoptosis

Naive T cell

Antigens

T cell activation by a dendritic cell

Dendritic cellActivated T cell

Antigen

CD28 CD80/86

T cell inhibition by tumor cell

Inhibited T cell Tumor cell – Growing

Activated T cell Tumor cell – Dying

T cell activation by immunotherapy

Tumor cellActivated T cell

Tumor cell death

T cell inhibition by a dendritic cell

PDL1PD1

Dendritic cell

Inhibited T cell

Antigen Presenting Cell T Cell T Cell Regulation

PD-L1 PD-1 Inhibition

PD-L2 PD-1 n/a

CD80 / CD86 CD28 Activation

CD80 / CD86 CTLA4 Inhibition

B7RP1 (ICOSL) ICOS Activation

B7-H3 (CD276) n/a Inhibition

B7-H4 (VTCN1) n/a Inhibition

B7-H5 CD28H Activation

n/a VISTA Inhibition

HVEM BTLA Inhibition

CD40 CD40L Activation

OX40L OX40 Activation

CD137L CD137 Activation

CD70 CD27 Activation

GAL9 TIM3 Inhibition

GITRL GITR Activation

MHC-II LAG-3 Inhibition

Cancer immunity cycle

T cell activation is regulated by stimulatory and inhibitory signals that fine-tune the immune response. The key to a successful therapy would require a balance between recognition and destruction of tumor cells, and inappropriate over-stimulation of immune responses.Please see the table for a list of targets that regulate T cell activation.

T cells are inhibited when– T cell receptors bind to inhibitory receptors on

antigen presenting cells (APCs)– Through these interactions the immune

system is regulated to minimize autoimmune inflammation

Regulators of T cell activation*

Blocking the T cell inhibitiory signal leads to an active immune response against the cancer cells and causes tumor cell death.

T cells are activated when– A T cell receptor recognizes an antigen on the

surface of the antigen presenting cell (APC)

– Co-stimulatory interaction occurs between T cells and APCs

Cancer immunotherapy strategies involve blocking key immune checkpoint inhibitors to ensure immune responses remain effective against cancer. Immunotherapies against CTLA-4 and PD-1 reveal promising results against some cancer types.

PD-1/PD-L1 interaction reduces cytokine production and suppresses T cell proliferation. Tumor cells exploit this immune checkpoint pathway as a mechanism to evade detection and inhibit the anti-tumor immune response. This leads to cancer progression.

PD-L1 [28-8] RabMAb® knockout-validated antibodyKey features- Knockout (KO) cell line-validated in key applications: IHC, FC, WB

- Highly specific for human PD-L1; no cross-reactivity with human PD-L2

- Tested with pathologically-validated positive and negative controls

- Generated using extracellular domain of PD-L1 protein – observed membrane specific staining

- Extensive validation in automated protocols1 (Phillips et al., 2015)

Reference1. Phillips, T. et al. Development of an automated PD-L1 immunohistochemistry (IHC) assay for non-small cell lung cancer. Appl Immunohistochem Mol Morphol 23, 541–549 (2015).

B-CAP Cells – high HCC70 Cells – medium ES-2 Cells – low COLO205 Cells – none(Cancer cell lines with varying levels of PD-L1 expression)

Wild type L2987 cells PD-L1 KO L2987 cells