Cancer immunotherapy - Immune checkpoint
T cell activation is regulated by stimulatory
and inhibitory signals that fine-tune the
response and maintain the balance
between appropriate recognition and
destruction of tumors and inappropriate
overstimulation of immune responses.
Please see the table for a list of targets
that regulate T cell activation.
CD28
T cell is activated when:
CD80/86
T-cell receptor recognizes an antigen on the surface
of the antigen presenting cell (APC).
Activated T cell
Dendritic cell
Co-stimulatory interaction occurs between T cell
and APC.
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 immune response.
This leads to cancer progression.
Antigen
TCR
T cell activation by dendritic cell
Tumor cell - Growing
Inhibited T cell
Activated T cell
Inhibited T cell
PD1
PDL1
Dendritic cell
T cell inhibition by tumor cell
Naive T cell
T cell activation
PDL1
PD1
T cell inhibition by dendritic cell
T cell proliferation
T cell priming
Activated T cell
T cell is inhibited when:
Cancer immunity cycle
Co-inhibitors of T cell are bound to their receptors
on APC.
Cancer immunotherapy strategies involve
blocking of key immune checkpoint inhibitors
to ensure immune responses remain effective
against cancer. Immunotherapies against PD-L1
and PD-1 reveal promising results against some
cancer types.
Through these interactions the immune system is
regulated to minimize autoimmune inflammation.
Dendritic 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
Copyright © 2015 Abcam, All rights reserved. RabMAb® is a registered trademark of Abcam. *Adapted from Pardoll, et al., 2012
Tumor cell
Antigens
T cell activation by immunotherapy
Tumor apoptosis
PD-L1 [28-8] RabMAb® knockout validated antibody
Blocking PD-L1 with a monoclonal antibody interferes
with T cell inhibition and active immune response leads
to tumor cell death.
Activated T cell
Tumor cell
Key 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
Wild Type L2987 Cells
PD-L1 KO L2987 Cells
Tested with pathologically validated positive and negative controls
Generated using extracellular domain of PD-L1 protein – observed
membrane specific staining
Tumor cell death
Extensive validation in automated protocols (Phillips et al., 2015)
Reference
B-CAP Cells - High
Discover more at abcam.com/cancer
Antigen capture
Tumor cell - Dying
HCC70 Cells - Medium ES-2 Cells - Low
COLO205 Cells - None
(Cancer cell lines with varying levels of PD-L1 expression)
Phillips, T., Simmons, P., Inzunza, H., Cogswell, J., Novotny, J., Taylor, C. and Zhang, X. (2015).
Development of an Automated PD-L1 Immunohistochemistry (IHC) Assay for Non–Small Cell
Lung Cancer. Applied Immunohistochemistry & Molecular Morphology, 23(8), pp.541-549.
E-914
Regulators of T cell activation*
Activated T cell
Tumor infiltration