Immune checkpoint PD-L1 immunohistochemical detection method and result judgment

In 2011, the FDA approved the first tumor immune checkpoint inhibitor, ipilimumab, a CTLA-4 blockade inhibitor, for the treatment of melanoma

 

Therefore, it is particularly important to understand immune checkpoints, immune checkpoint inhibitors, detection molecular markers, detection methods and criteria

Therefore, it is particularly important to understand immune checkpoints, immune checkpoint inhibitors, detection molecular markers, detection methods and criteria

1.

1.

PD-L1 (programmed death ligand 1) is a ligand for programmed death receptor 1 and a ligand for PD-1 (programmed cell death 1, programmed death receptor 1)

PD-L1 (programmed death ligand 1) is a ligand for programmed death receptor 1 and a ligand for PD-1 (programmed cell death 1, programmed death receptor 1)

Cancer cells suppress T cells through PD-L1

Cancer cells suppress T cells through PD-L1

 

PD-1 belongs to a transmembrane protein on the cell membrane and is expressed on immune cells such as T cells and B cells as well as tumor cells.

PD-1 belongs to a transmembrane protein on the cell membrane and is expressed on immune cells such as T cells and B cells as well as tumor cells.

​

PD1 signaling pathway

PD1 signaling pathway

 

2.

2.

Immune checkpoint inhibitors can combine with PD-1 or PD-L1 to block the control of immune function by tumor cells, ensure the function of immune cells such as T cells, and regain the clearance effect of T cells on tumors

Immune checkpoint inhibitors can combine with PD-1 or PD-L1 to block the control of immune function by tumor cells, ensure the function of immune cells such as T cells, and regain the clearance effect of T cells on tumors.

 

3.

3.

PD-L1 immunohistochemical detection is a simple and effective method to predict the efficacy of PD-1 or PD-L1 .

PD-L1 immunohistochemical detection is a simple and effective method to predict the efficacy of PD-1 or PD-L1 .
It detects the expression of PD-L1 on the surface of tumor cells (TC) or immune cells (IC) , and then speculates Methods of efficacy of PD-L1 inhibitors
.
Predicting PD-1 or PD-L1 efficacy on tumor cells (TC) or immune cells (IC)

 

At present, there are five commonly used immunohistochemical detection antibodies for PD-L1: 22C3, 28-8, SP263, SP142 and 73-10, as well as E1L3N commonly used in the laboratory
.

At present, there are five commonly used immunohistochemical detection antibodies for PD-L1: 22C3, 28-8, SP263, SP142 and 73-10, as well as E1L3N commonly used in the laboratory
.
22C3, 28-8, SP263, SP142 and 73-10, as well as E1L3N commonly used in the laboratory
.

 

Four PD-L1 detection antibodies

Four PD-L1 detection antibodies

 

Different antibodies need to be detected with different detection platforms.
The mainstream detection platforms are 4 antibody detection platforms of the two companies, namely the AutoStainer Link 48 platform for DAKO 22C3 and 28-8 detection, and the Ventana Benchmark Ultra platform for Ventana SP142 and SP263 detection
.

Different antibodies need to be detected with different detection platforms.
The mainstream detection platforms are 4 antibody detection platforms of the two companies, namely the AutoStainer Link 48 platform for DAKO 22C3 and 28-8 detection, and the Ventana Benchmark Ultra platform for Ventana SP142 and SP263 detection
.

 

 

Fourth, the determination of immunohistochemical test results

4.
Judgment of immunohistochemical test results 4.
Judgment of immunohistochemical test results

 

In addition to tumor cells (TC) expressing PD-L1, tumor-infiltrating immune cells (IC) also express PD-L1, so whether the content of these immune cells should be considered when defining the positive rate of PD-L1, tumor cells (TC) ) On the surface of PD-L1 and on the surface of immune cells (IC), which one is more suitable as a criterion for predicting the effect of PDL1 inhibitors?

In addition to tumor cells (TC) expressing PD-L1, tumor-infiltrating immune cells (IC) also express PD-L1, so whether the content of these immune cells should be considered when defining the positive rate of PD-L1, tumor cells (TC) ) On the surface of PD-L1 and on the surface of immune cells (IC), which one is more suitable as a criterion for predicting the effect of PDL1 inhibitors?

 

Therefore, for the determination of the positive rate of PD-L1, different companies use different methods for testing, and the standards for each method are also different
.
The determination methods used for PD-L1 detection antibodies include TPS, CPS, and calculation of TC and IC respectively
.
The main difference between different interpretation methods is whether to count the number of positive immune cells in the tumor area
.

Therefore, for the determination of the positive rate of PD-L1, different companies use different methods for testing, and the standards for each method are also different
.
The determination methods used for PD-L1 detection antibodies include TPS, CPS, and calculation of TC and IC respectively
.
The main difference between different interpretation methods is whether to count the number of positive immune cells in the tumor area
.
The determination methods used for PD-L1 detection antibodies include TPS, CPS, and calculation of TC and IC respectively
.

 

TPS is concerned with the expression of PD-L1 on the surface of tumor cells (TC).
CPS is a tumor cell with positive comprehensive membrane staining, and the number of lymphocytes and macrophages directly related to tumor cells, relative to the proportion of tumor cells (at least 100).
Fraction (CPS is a numerical value, not a %)
.

TPS is concerned with the expression of PD-L1 on the surface of tumor cells (TC).
CPS is a tumor cell with positive comprehensive membrane staining, and the number of lymphocytes and macrophages directly related to tumor cells, relative to the proportion of tumor cells (at least 100).
Fraction (CPS is a numerical value, not a %)
.
TPS is concerned with the expression of PD-L1 on the surface of tumor cells (TC).
CPS is a tumor cell with positive comprehensive membrane staining, and the number of lymphocytes and macrophages directly related to tumor cells, relative to the proportion of tumor cells (at least 100).
Fraction (CPS is a numerical value, not a %)
.

 

1.
TPS: Tumor Proportion Score

1.
TPS: Tumor Proportion Score 1.
TPS: Tumor Proportion Score

 

TPS=(PD-L1 membrane staining positive tumor cells/total tumor cells)×100%

TPS=(PD-L1 membrane staining positive tumor cells/total tumor cells)×100% TPS=(PD-L1 membrane staining positive tumor cells/total tumor cells)×100%

 

2.
CPS: Combined Positive Score

2.
CPS: Combined Positive Score 2.
CPS: Combined Positive Score

 

CPS=(PD-L1 membrane staining positive tumor cells + PD-L1 membrane staining positive tumor-associated immune cells (lymphocytes, macrophages))/total tumor cells x 100

CPS=(PD-L1 membrane staining positive tumor cells + PD-L1 membrane staining positive tumor-associated immune cells (lymphocytes, macrophages))/total number of tumor cells x 100 CPS=(PD-L1 membrane staining positive tumor cells + PD -L1 membrane staining positive tumor-associated immune cells (lymphocytes, macrophages))/total tumor cells x100

 

3.
TC: tumor cell positive rate

3.
TC: tumor cell positive rate 3, TC: tumor cell positive rate

 

TC=(any intensity of PD-L1 membrane staining positive tumor cells/total tumor cells) x 100%

TC=(any intensity of PD-L1 membrane staining positive tumor cells/total tumor cells) x 100% TC=(any intensity PD-L1 membrane staining positive tumor cells/total tumor cells) x 100%

 

4.
IC: positive rate of tumor-related immune cells

4.
IC: positive rate of tumor-related immune cells 4.
IC: positive rate of tumor-related immune cells

 

IC = (number of tumor-associated immune cells with positive PD-L1 membrane staining at any intensity/total number of tumor-associated immune cells) x 100%

IC=(Number of tumor-associated immune cells with positive PD-L1 membrane staining at any intensity/total tumor-associated immune cells) x 100% IC=(Number of tumor-associated immune cells with positive PD-L1 membrane staining at any intensity/total tumor-associated immune cells Number) x100% 5.
PD-L1 criteria for approved immune checkpoint inhibitors 5.
PD-L1 criteria for approved immune checkpoint inhibitors Companion diagnostics for nivolumab , Dako 28-8 and Ventana SP142 are complementary diagnostics for nivolumab and atezolizumab, respectively
.
Ventana SP263 is approved by the European Union as a complementary diagnostic for three immunosuppressants
.
Diagnosis Dako 28-8 and Ventana SP142 are complementary diagnoses for nivolumab and atezolizumab, respectively

PD-L1 IHC 22C3 PharmDx (DAKO) immunohistochemistry has been approved by the U.
S.
Food and Drug Administration (FDA) as a companion diagnostic for KEYTRUDA® (pembrolizumab, a PD-1 inhibitor) in the treatment of tumors such as non-small cell lung cancer

PD-L1 IHC 22C3 PharmDx (DAKO) immunohistochemistry has been approved by the U.
S.
Food and Drug Administration (FDA) as a companion diagnostic for KEYTRUDA® (pembrolizumab, a PD-1 inhibitor) in the treatment of tumors such as non-small cell lung cancer PD-L1 IHC 22C3 PharmDx (DAKO) immunohistochemistry has been approved by the U.
S.
Food and Drug Administration (FDA) as a companion diagnostic for KEYTRUDA® (pembrolizumab, a PD-1 inhibitor) in the management of tumors such as non-small cell lung cancer

 

PD-L1 IHC SP263 (Ventana) immunohistochemistry has been approved by the FDA for complementary diagnosis of the following tumor immunotherapy drugs

PD-L1 IHC SP263 (Ventana) immunohistochemistry has been approved by the FDA for the supplemental diagnosis of the following tumor immunotherapy drugs PD-L1 IHC SP263 (Ventana) immunohistochemistry has been approved by the FDA for the supplementary diagnosis of the following tumor immunotherapy drugs tumor immunity

 

 

PD-L1 IHC SP142 (Ventana) immunohistochemistry has been approved by the FDA and recommended as a companion diagnostic for the following tumor immunotherapy drugs

PD-L1 IHC SP142 (Ventana) immunohistochemistry has been approved by the FDA and recommended for use as a companion diagnostic for the following tumor immunotherapy drugs PD-L1 IHC SP142 (Ventana) immunohistochemistry has been approved by the FDA and recommended for the following tumor immunotherapy drugs companion diagnosis

 

 

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