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Updated: Jul 11, 2025

Orthotopic Transplantation of Syngeneic Lung Adenocarcinoma Cells to Study PD-L1 Expression
Published on: January 19, 2019
Immunotherapy and lung cytopathology: Overview and possibilities
Maria D Lozano1,2,3, Allan Argueta1, Carlos de Andrea1,2,3,4
1Department of Pathology, Clínica Universidad de Navarra, University of Navarra, Pamplona, Spain.
Insights
Immunotherapy shows promise for cancer treatment, with PD-L1 testing crucial for evaluation. This review explores cytopathology
Area of Science:
- Oncology and Pathology
- Cancer Immunotherapy Research
Background:
- Immunotherapy has emerged as a significant cancer treatment modality.
- Immunohistochemistry (IHC) is the standard for Programmed Death-Ligand 1 (PD-L1) and Programmed Death 1 (PD1) evaluation.
- PD-L1 assays are applicable to both formalin-fixed paraffin-embedded (FFPE) tissues and cytological samples, but validation on smears is ongoing.
Purpose of the Study:
- To review the role of cytopathology in analyzing PD-L1 expression using immunocytochemistry (ICC).
- To explore future directions for cytopathology in the context of cancer immunotherapy.
- To highlight the potential of advanced imaging and algorithms for PD-L1 interpretation in cytological specimens.
Main Methods:
- Review of existing literature on PD-L1 testing in cytological samples.
- Discussion of immunohistochemistry (IHC) and immunocytochemistry (ICC) techniques for PD-L1 evaluation.
- Exploration of multiplexed immunofluorescence (mIF) assays on minimally invasive cytological samples.
Main Results:
- While IHC is established, the application of PD-L1 assays on cytological smears requires further validation.
- Digital imaging and algorithms offer potential for improved interpretation of PD-L1 in cytological samples.
- Multiplexed immunofluorescence (mIF) on cytological samples is a promising approach for studying the tumor immune microenvironment in non-small cell lung cancer (NSCLC).
Conclusions:
- Cytopathology plays an increasingly important role in evaluating biomarkers for immunotherapy.
- Further research and validation are needed to optimize PD-L1 testing on cytological specimens.
- Advanced techniques like mIF hold promise for comprehensive immune profiling in NSCLC.
Abstract:
Immunotherapy has become a promising cancer treatment in the past decade, and IHC is the most commonly used testing method for PDL-1/PD1 evaluation. In general, PD-L1 assays can be performed on both FFPE specimens and cytological samples. However, their use on smears is not yet well-established or validated. Nowadays, digital images and advanced algorithms can aid in interpreting PD-L1 in cytological samples. Understanding the immune environment of non-small cell lung cancer (NSCLC) is critical in developing successful anticancer immunotherapies. The use of a multiplexed immunofluorescence (mIF) assay on cytological samples obtained through minimally invasive methods appears to be a viable option for investigating the immune environment of NSCLC. This review aims to briefly summarize the knowledge of the role of cytopathology in the analysis of PD-L1 by immunocytochemistry (ICC) and future directions of cytopathology in the immunotherapy setting.
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