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Updated: Aug 24, 2025
Multiplexed Immunofluorescence Analysis and Quantification of Intratumoral PD-1+ Tim-3+ CD8+ T Cells
Published on: February 8, 2018
Programmed cell death 1 and programmed cell death ligand 1 expression in invasive breast carcinoma using CAL10 and
Özlem Durak1, Kemal Kürşat Bozkurt2, İbrahim Metin Çiriş2
1Department of Pathology, Kastamonu State Hospital, Kastamonu, Turkey.
Abstract:
Increased incidence of breast cancer has stimulated development of new diagnostic and therapeutic methods. The programmed cell death 1 (PD1) pathway and its inhibitors are promising avenues for investigation. PD1 includes PD ligands 1 (PDL1) and 2 (PDL2). We investigated the expression of PD1 and PDL1 in invasive breast carcinomas using immunohistochemical staining. We used 171 invasive breast carcinoma specimens from which tissue microarray blocks were created. Immunohistochemical staining of PD1 using NAT105, and PDL1 using CAL10 was performed on tissue microarray sections. NAT105 and CAL10 are useful clones for detecting expression of PD1 and PDL1. PD1 and PDL1 immunostaining was significantly stronger in carcinomas with basal-like phenotype compared to other molecular breast cancer types. PD1 and PDL1 expression also was associated with a high histologic grade and a high Ki-67 index. PD1 expression also was associated with lymphovascular invasion and axillary metastasis. PD1 and PDL1 expression is associated with aggressive tumor behavior and a basal-like phenotype in breast cancer. We suggest that inhibition of the PD1/PDL1 pathway, particularly in triple negative breast carcinomas with basal-like phenotype, might be useful for targeted immunotherapy.
Insights
Programmed cell death 1 (PD1) pathway proteins were more expressed in aggressive breast cancers. Targeting this PD1/PDL1 pathway may offer new immunotherapy options for triple-negative breast cancer.
Area of Science:
- Oncology
- Immunology
- Pathology
Background:
- Breast cancer incidence is rising, driving the need for novel diagnostic and therapeutic strategies.
- The programmed cell death 1 (PD1) pathway, including its ligands PDL1 and PDL2, presents a promising target for cancer therapy.
- Understanding PD1 and PDL1 expression in breast cancer is crucial for developing targeted immunotherapies.
Purpose of the Study:
- To investigate the expression of PD1 and PDL1 in invasive breast carcinomas.
- To correlate PD1 and PDL1 expression with distinct molecular subtypes, histologic grade, and clinical features of breast cancer.
- To evaluate the potential of PD1/PDL1 pathway inhibition as a targeted immunotherapy approach.
Main Methods:
- Utilized immunohistochemical staining on 171 invasive breast carcinoma specimens.
- Employed tissue microarray techniques for standardized analysis.
- Assessed PD1 expression using the NAT105 clone and PDL1 expression using the CAL10 clone.
Main Results:
- PD1 and PDL1 immunostaining intensity was significantly higher in basal-like breast carcinomas compared to other molecular subtypes.
- Elevated PD1 and PDL1 expression correlated with high histologic grade and high Ki-67 proliferation index.
- PD1 expression was associated with lymphovascular invasion and axillary metastasis, indicating aggressive tumor behavior.
Conclusions:
- PD1 and PDL1 expression is linked to aggressive tumor behavior and the basal-like phenotype in breast cancer.
- The PD1/PDL1 pathway represents a potential therapeutic target, especially for triple-negative breast carcinomas with a basal-like phenotype.
- Targeted immunotherapy via PD1/PDL1 pathway inhibition may offer a novel treatment strategy for specific breast cancer subtypes.
