PDCD1 Antibody
Product Specs
Target Background
- HLA-G, NRP1, and PD-1 may be involved in the immune response in psoriatic patients. PMID: 29790686
- The proportions of naive CD4+ T cells were lower in young melanoma patients compared to age-matched controls, but comparable to those in older patients and controls. This reduction in naive CD4+ T cells was accompanied by an increase in memory CD4+ T cells expressing HLA-DR, Ki-67, and PD-1 in young melanoma patients compared to age-matched controls, but not in older patients. PMID: 29546435
- A meta-analysis has revealed that the PD-1 rs36084323 A > G polymorphism is associated with a decreased risk of cancer in Asian populations. PMID: 30249505
- A study conducted in Southern Brazil found no significant association between the PD1.3G/A - rs11568821 polymorphism and susceptibility to systemic lupus erythematosus or rheumatoid arthritis. PMID: 27914594
- SLC18A1 might complement other biomarkers currently under investigation in relation to programmed cell death protein 1/programmed cell death protein ligand 1 (PD-1/PD-L1) inhibition. PMID: 30194079
- Structural and functional analyses unexpectedly revealed an N-terminal loop outside the IgV domain of PD-1. This loop is not involved in the recognition of PD-L1 but plays a dominant role in binding to nivolumab, while N-glycosylation is not involved in binding at all. PMID: 28165004
- Findings suggest the potential therapeutic application of PD-1 blockade in acute myeloid leukemia (AML). Research demonstrated an excellent synergistic therapeutic effect when combining PD-1 blockade with CTL therapy compared to either treatment alone. PMID: 29962321
- High PD-1 expression is associated with Mycobacterium avium complex-induced lung disease. PMID: 28169347
- PD-1/PD-L1 expression is frequently observed in poorly differentiated neuroendocrine carcinomas of the digestive system. PMID: 29037958
- Research indicates that high-level PD1 expression may be a significant factor associated with the immune checkpoint pathway in liver cancer. PMID: 29620156
- Studies suggest that the PD-1 genotype of the donor plays a critical role in the development of acute graft-versus-host disease (GvHD) after allogeneic hematopoietic stem cell transplantation (alloHSCT) from HLA-identical sibling donors. PMID: 30019128
- A subgroup of advanced disease ovarian cancer patients with high-grade tumors expressing PD-L1 may be prime candidates for immunotherapy targeting PD-1 signaling. PMID: 29843813
- Both rs2227982 and rs2227981 polymorphisms were associated with type 1 diabetes (T1D) risk in East Asians, and rs2227982 also showed a significant association with glycemic traits, suggesting that PDCD1 gene polymorphisms might contribute to T1D risk. [meta-analysis] PMID: 29774466
- The PD.1 (-538G/A) gene polymorphism is associated with colon cancer risk. PMID: 29580042
- The high-affinity PD-1 mutant could compete with the binding of antibodies specific to PD-L1 or PD-L2 on cancer cells. PMID: 29890018
- The G allele of rs36084323 of PDCD1 is associated with an increased risk of advanced TNM staging of colorectal cancer. PMID: 29652996
- Promoter methylation of CTLA4, PD-L1, PD-L2, and PD-1 in diffuse lower-grade gliomas (LGG) harboring isocitrate dehydrogenase (IDH) mutation has been reported. PMID: 29396294
- Unlike other multiple autoimmune disease-associated genetic variants, there was no association between PDCD1 variants and Juvenile Idiopathic Arthritis. PMID: 28056736
- Alteration of the PD-1/PD-L1 pathway can modulate Treg/Th17 balance in asthmatic children. PMID: 29874664
- The expression of PD1 on T cells was elevated in patients with rheumatoid arthritis and correlated with disease activity. PMID: 29257239
- High expression of programmed death-1 in sentinel lymph nodes is associated with breast cancer. PMID: 29193094
- Three cases are described of patients with metastatic renal cell carcinoma (mRCC) treated with anti-PD-1 antibody therapy in combination with targeted therapy (bevacizumab), anti-cytotoxic T lymphocyte antigen 4 therapy (ipilimumab), or radiotherapy. PMID: 29146617
- Anti-CTLA4/anti-PD-1/PD-L1 combinations versus anti-PD-1/PD-L1 monotherapy were found to be an independent factor, aside from tumor mutational burden (TMB), for predicting a better response rate (77% vs. 21%; P = 0.004) and progression-free survival (P = 0.024). Higher TMB predicts a favorable outcome to PD-1/PD-L1 blockade across diverse tumors. PMID: 28835386
- The altered soluble (s)PD1 and sICOS serum levels in the different Hepatitis B (HBV) groups may reflect the dysregulation of T cell activation and may be associated with the HBV pathological process. PMID: 28983583
- PD-L1 expression was upregulated following TGF-beta induction but downregulated by TGF-beta receptor-kinase inhibitors and the mesenchymal-to-epithelial transition (MET) process. Moreover, chemotherapy treatment increased TGF-beta expression and enhanced PD-L1 expression via autocrine TGF-beta-induced EMT. Analysis of clinical samples revealed a significant relationship between PD-L1 expression and EMT status. PMID: 28849209
- This study demonstrated that PD-1 may be involved in lymph node metastasis and provides further insight into the mechanism of immunotherapies in non-small cell lung cancer. PMID: 28799818
- PD-L1 expression in melanoma tumor cells is lower than in non-small cell lung cancer (NSCLC) or renal cell carcinoma cells. The higher response rate in melanoma patients treated with PD-1 inhibitors is likely related to PD-L1 expression in tumor-associated inflammatory cells. Further studies are needed to validate the predictive role of inflammatory cell PD-L1 expression in melanoma and determine its biological significance. PMID: 28223273
- A higher proportion of pre-treatment PD-1(+) T cells in responders suggests active suppression of an engaged immune system that is disinhibited by anti-PD-1 therapies. Furthermore, immunoprofiling of end-of-treatment (EDT) biopsies for increased PD-L1 expression and immune cell infiltration showed greater predictive utility than pre-treatment (PRE) biopsies and may allow for a better selection of patients most likely to benefit from anti-PD-1 therapies, warranting further evaluation. PMID: 28512174
- PD-1 was overexpressed on CD8+ T-cells from patients with obstructive sleep apnea in a severity-dependent manner. PMID: 29051270
- Research has shown that the distinctive pathological features of papillary thyroid carcinomas (PTCs), including tumor-infiltrating lymphocytes (TILs), background chronic lymphocytic thyroiditis (CLT), female gender, psammoma bodies, and stromal calcification, are useful parameters for predicting PD-L1 or PD-1 expression. PMID: 28974264
- No association was found between PDCD1 SNPs and the development of juvenile idiopathic arthritis in an Iranian population. PMID: 29307156
- High expressions of programmed cell death protein 1 (PD-1) and programmed cell death 1 ligand 1 (PD-L1) were associated with poor prognosis after surgery. PMID: 29848685
- Programmed death-1 polymorphism is associated with the risk of esophagogastric junction adenocarcinoma. PMID: 28487496
- PD-1 was expressed in 26% of Ewing's sarcoma family of tumor cells and may have prognostic and therapeutic implications. PMID: 29445891
- Patients with low PD-L1 expression on myeloid cells have improved survival when treated with an antitumor vaccine, suggesting that PD-L1 expression on myeloid cells may be an important predictive biomarker in future clinical trials. Additionally, the combination of PD-1/PD-L1 inhibition and vaccination may enhance the efficacy of this immunotherapeutic approach. PMID: 28193626
- Lower expression of PD-1 and PD-L1 was associated with better survival in patients who underwent surgery for the primary tumor and had multiple brain metastases. PMID: 28201746
- The PD-1/PD-L pathway inhibits Mycobacterium tuberculosis-specific CD4(+) T-cell functions and phagocytosis of macrophages in active tuberculosis. PMID: 27924827
- This study provides optimism that harmonization between assays may be achievable, and that the three assays studied could potentially be used interchangeably to identify patients most likely to respond to anti-PD-1/PD-L1 immunotherapies, provided that the appropriate clinically defined algorithm and agent are always linked. PMID: 28073845
- Results identified an overall low expression of PD-1 and PD-L1 in high-risk prostate cancer tissue. PMID: 28461179
- Biopsy tumor key protein measurements demonstrate substantial between-tumor variation in expression ratios of these proteins and suggest that programmed cell death 1 ligand 2 (PD-L2) is present in some tumors at levels sufficient to contribute to programmed cell death-1 (PD-1)-dependent T-cell regulation and possibly to affect responses to PD-1- and programmed cell death 1 ligand 1 (PD-L1)-blocking drugs. PMID: 28546465
- Early phase clinical trials using PD-1 or PD-L1 inhibitors alone or in combination have shown objective tumor responses and durable long-term disease control in heavily pre-treated patients, notably in the triple-negative (TN) subtype. Blockade of PD-1 or PD-L1 shows impressive antitumor activity in some subsets of breast cancer patients. PMID: 28799073
- Differential expression of immunological markers relating to the PD-1/PD-L1 pathway in blood can be used as potential diagnostic and prognostic markers in ovarian cancers. These data have implications for the development and trial of anti-PD-1/PD-L1 therapy in ovarian cancer. PMID: 27986748
- LAG-3+ tumor-infiltrating lymphocytes (iTILs) are enriched in estrogen receptor-negative breast cancers and represent an independent favorable prognostic factor. In addition, a high proportion of PD-1/PD-L1+ tumors are co-infiltrated with LAG-3+ TILs. PMID: 29045526
- An IDO1 inhibitor, epacadostat, also demonstrated promising activity in combination with the PD-1 checkpoint inhibitors in other solid tumors, including melanoma, urothelial carcinoma, renal cell carcinoma, and non-small cell lung cancer. PMID: 28760910
- PD-L1 was positive in tumor cells in 2/13 cases, weak positive in 7/13, and negative in 4/13 cases, respectively. PMID: 28807336
- This report presents the first case of immune microenvironment profiling and response to anti-PD-1 in a patient with renal medullary carcinoma, suggesting that anti-PD-1-based therapies may have clinical activity in this disease. PMID: 28105368
- Two cases of metastatic melanoma treated with nivolumab and pembrolizumab (anti-PD-1) are presented. Both patients developed acute interstitial nephritis during immune checkpoint therapy. PMID: 28105370
- The positive rate of PD-L2 did not show any differences between primary tumors and metastatic lymph nodes. In multivariate analysis, PD-L1 expression, PD-L2 expression, a low density of CD8(+) T cells in primary tumors, and PD-1 expression on CD8(+) T cells in primary tumors were associated with poor prognosis. PMID: 28754154
- Relative to controls, the expression of PD-1 and PD-L1 on peripheral blood and tumor infiltrating T cells increased with disease progression. Upregulation of expression promotes T-cell apoptosis in gastric adenocarcinoma. PMID: 29599324
- These data support the combinatorial approach of in situ suppression of the PD-L inhibitory checkpoints with dendritic cell (DC)-mediated IL15 transpresentation to promote antigen-specific T-cell responses and ultimately contribute to graft-versus-tumor immunity. PMID: 28637876
Q&A
What is the mechanism of action for PDCD1 antibodies in immune regulation?
PDCD1 delivers inhibitory signals upon binding to ligands CD274/PDCD1L1 and CD273/PDCD1LG2. Following T-cell receptor (TCR) engagement, PDCD1 associates with CD3-TCR in the immunological synapse and directly inhibits T-cell activation. It suppresses T-cell activation through the recruitment of PTPN11/SHP-2; following ligand-binding, PDCD1 is phosphorylated within the ITSM motif, leading to the recruitment of protein tyrosine phosphatase PTPN11/SHP-2 that mediates dephosphorylation of key TCR proximal signaling molecules, such as ZAP70, PRKCQ/PKCtheta and CD247/CD3zeta . The PDCD1-mediated inhibitory pathway is exploited by tumors to attenuate anti-tumor immunity, facilitating tumor survival. Anti-PD1 antibodies block this pathway, reinstating T cell effector functions.
What are the common applications for PDCD1 antibodies in laboratory research?
PDCD1 antibodies are extensively used in multiple research applications:
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Immunohistochemistry (IHC-P) for tissue section analysis
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Flow Cytometry for cell surface expression detection
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ELISA for quantitative measurement
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Western Blotting for protein detection
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Immunofluorescence for cellular localization studies
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Functional assays to evaluate T-cell responses
The most commonly reported application is Flow Cytometry, with over 4400 citations in the literature describing PDCD1 antibody use in research .
What cell types and tissues typically express PDCD1 for antibody detection?
PDCD1 is notably expressed in lymphoid tissues, particularly lymph nodes and tonsils . It serves as a marker for identifying specific immune cell populations:
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T Follicular Helper Cells
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T Follicular Regulatory Cells
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Activated T cells
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Exhausted T cells in tumor microenvironments
For optimal detection, researchers should examine tissues where PDCD1 expression is highest, such as tonsil tissue, which serves as an excellent positive control for PDCD1 antibody validation .
How can researchers establish an imaging system to evaluate PDCD1 antibody efficacy?
Researchers can establish advanced imaging systems to visualize human PD-1 microclusters and evaluate antibody efficacy. A documented approach involves:
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Creating a system where a minimal T cell receptor (TCR) signaling unit co-localizes with PDCD1
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Utilizing super-resolution imaging to observe microcluster formation by human PD-1
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Evaluating how blocking antibodies inhibit PD-1-PD-L1 binding and microcluster formation
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Measuring the concentration-dependent effects of therapeutic antibodies (pembrolizumab, nivolumab, durvalumab, atezolizumab)
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Digitally evaluating PDCD1-mediated T cell suppression to assess clinical usefulness
This imaging approach allows for direct visualization of antibody effects on PDCD1 function rather than simple binding assays.
What factors influence reproducibility in PDCD1 antibody-based experiments?
Several critical factors affect reproducibility in PDCD1 antibody experiments:
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Antibody selection: Clone specificity, host species, and antibody format (monoclonal vs. polyclonal)
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Sample preparation: Fixation methods significantly impact epitope availability (boiling tissue sections in 10 mM Tris with 1 mM EDTA, pH 9.0, for 10-20 min followed by cooling at RT for 20 minutes is recommended for some antibodies)
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Antibody validation: Using appropriate positive controls (like TY cells or tonsil tissue)
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Protocol optimization: Concentration titration (typically 1-2 μg/mL for IHC applications)
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Detection systems: Fluorescent conjugates vs. enzymatic detection methods
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Cross-reactivity considerations: Especially important when working with different species
For consistent results, researchers should validate each antibody lot and optimize conditions for their specific experimental system.
How do PDCD1 polymorphisms influence response to anti-PD1 therapies?
PDCD1 polymorphisms may serve as predictive biomarkers for anti-PD1 therapy response. A retrospective analysis of plasma DNA from patients with advanced melanoma treated with PD-1 antibodies revealed that:
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Patients with the G/G genotype of PD1.3 rs11568821 had more complete responses than those with A/G genotype (16.5% vs. 2.6% respectively)
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The G allele of PD1.3 rs11568821 was significantly associated with a longer median progression-free survival (PFS) than the AG allele (14.1 vs. 7.0 months, p=0.04; 95% CI 0.14–0.94)
This suggests that germline PDCD1 polymorphisms should be considered alongside tumor intrinsic factors as predictive biomarkers for immune checkpoint regulators in clinical applications.
What biomarkers correlate with response to PDCD1-targeted therapies?
Several biomarkers have demonstrated correlations with response to anti-PDCD1 therapy:
| Biomarker | Association with Response | Limitations |
|---|---|---|
| PD-L1 expression | Positively correlated with response in several cancer types | Heterogeneous expression, variable cutoffs, dynamic nature |
| Tumor Mutation Burden (TMB-H) | Strongly associated with response | ~5% of low TMB patients respond well; >50% of TMB-H patients do not respond |
| Defective DNA mismatch repair (dMMR) | Associated with better response | Limited predictive capacity as sole marker |
| High microsatellite instability (MSI-H) | Predictive of response in multiple cancer types | Limited sensitivity |
These genetic characteristics lead to high neoantigen load, facilitating immune recognition of the tumor and resulting in more potent anti-tumor responses following treatment . Interestingly, melanoma patients with moderate expression of PDL1 exhibited better response to anti-PD1 therapy than those with overexpression .
What are the critical steps for validating a new PDCD1 antibody for research use?
Validating a new PDCD1 antibody requires multiple steps:
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Specificity testing:
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Use known positive controls (tonsil tissue, activated T cells)
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Include appropriate negative controls
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Perform blocking experiments with recombinant PDCD1 protein
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Application-specific validation:
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For IHC: Test different antigen retrieval methods (e.g., boiling in 10mM Tris/1mM EDTA pH 9.0)
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For Flow Cytometry: Compare with established PDCD1 antibody clones
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For functional assays: Assess T-cell proliferation with and without antibody
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Cross-reactivity assessment:
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Test against related proteins (other checkpoint molecules)
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Evaluate species cross-reactivity if working with multiple models
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Reproducibility testing:
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Ensure lot-to-lot consistency
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Document optimal working concentrations for each application
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Functional validation:
How can PDCD1 antibodies be optimally used in T-cell functional assays?
For optimal use of PDCD1 antibodies in T-cell functional assays:
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Experimental setup:
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Co-culture activated T cells with target cells expressing PD-L1/PD-L2
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Add anti-PDCD1 antibodies at validated concentrations
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Include appropriate control antibodies (isotype controls)
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Key readouts:
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T-cell proliferation (measured by CFSE dilution or [3H]-thymidine incorporation)
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Cytokine production (IFN-γ, IL-2 by ELISA or intracellular cytokine staining)
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Cytotoxicity against target cells (51Cr release or flow-based assays)
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Optimization considerations:
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Antibody format matters: Soluble forms of some anti-PD1 antibodies (like PD1-17) enhance T-cell proliferation
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Co-engagement effects: Co-engagement by TCR and anti-PD-1 antibody PD1-17 or PD-L1-Fc reduces proliferation, while co-engagement by TCR and other antibodies (like J110) may not affect proliferation
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Concentration optimization: Each therapeutic antibody has a proprietary optimal concentration for maximum efficacy
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Advanced analysis:
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Combinatorial efficiency testing when using multiple checkpoint inhibitors
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Single-cell analysis for heterogeneous responses
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How are PDCD1 antibodies being used in combination therapy research?
PDCD1 antibodies are being investigated in combination with other therapeutic modalities:
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Combination with other checkpoint inhibitors:
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Combination with conventional cancer treatments:
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Sequential therapy approaches:
What are the challenges in interpreting contradictory PDCD1 antibody data across different tumor models?
Researchers face several challenges when interpreting contradictory data:
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Tumor heterogeneity factors:
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Technical variability:
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Varying IHC cut-offs to define PD-L1 positivity
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Different antibody clones may target different epitopes
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Staining of tumor versus immune cells provides different information
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Biological complexity:
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Experimental design considerations:
To address these challenges, researchers should employ multiple models, standardize technical approaches, and incorporate appropriate controls in their experimental designs.
