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Cancer immunotherapy - Immune checkpoint

T cell proliferation

T cell activation

T cell priming

Tumor infiltrationAntigen captureDendritic cell

Activated T cell

Activated T cell

Naive T cell

Tumor cell

Antigens

Tumor apoptosis

T cell activation by dendritic cell

Dendritic cell

Activated T cell

AntigenTCR

CD28CD80/86

T cell inhibition by tumor cell

PDL1

PD1

Tumor cell - GrowingInhibited T cell

T cell activation by immunotherapy

Activated T cell Tumor cell - Dying

Activated T cell

Tumor cell

Tumor cell death

T cell inhibition by dendritic cell

Dendritic cellInhibited T cell

PDL1PD1

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 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.

T cell is inhibited when:Co-inhibitors of T cell are bound to their receptors on APC.

Through these interactions the immune system is regulated to minimize autoimmune inflammation.

Regulators of T cell activation*

Blocking PD-L1 with a monoclonal antibody interferes with T cell inhibition and active immune response leads to tumor cell death.

T cell is activated when:T-cell receptor recognizes an antigen on the surfaceof the antigen presenting cell (APC).

Co-stimulatory interaction occurs between T cell and 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.

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.

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 protocols (Phillips et al., 2015)

ReferencePhillips, 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.

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