The Role of Pathology-Based Methods in Qualitative and Quantitative Approaches to Cancer Immunotherapy

Abstract

Immune checkpoint inhibitors, including those concerning programmed cell death 1 (PD-1) and its ligand (PD-L1), have revolutionised the cancer therapy approach in the past decade. However, not all patients benefit from immunotherapy equally. The prediction of patient response to this type of therapy is mainly based on conventional immunohistochemistry, which is limited by intraobserver variability, semiquantitative assessment, or single-marker-per-slide evaluation. Multiplex imaging techniques and digital image analysis are powerful tools that could overcome some issues concerning tumour-microenvironment studies. This novel approach to biomarker assessment offers a better understanding of the complicated interactions between tumour cells and their environment. Multiplex labelling enables the detection of multiple markers simultaneously and the exploration of their spatial organisation. Evaluating a variety of immune cell phenotypes and differentiating their subpopulations is possible while preserving tissue histology in most cases. Multiplexing supported by digital pathology could allow pathologists to visualise and understand every cell in a single tissue slide and provide meaning in a complex tumour-microenvironment contexture. This review aims to provide an overview of the different multiplex imaging methods and their application in PD-L1 biomarker assessment. Moreover, we discuss digital imaging techniques, with a focus on slide scanners and software.

Applicability of Spatial Technology in Cancer Research

“…Before routine implementation, thorough validation of the antibody panel is crucial. These include considerations such as staining order, marker co-localization, antibody elution, spectral overlap, antibody cross-reactivity, and potential signal reduction due to steric hindrance [12,24,26]. These measures ensure the reliability and accuracy of these technologies in identifying cellular phenotypes within specific tissue compartments such as the TME [75][76][77].…”

Exploring the Complex and Multifaceted Interplay between Melanoma Cells and the Tumor Microenvironment

“…Melanomas containing a high number of CD8+ T cells in the stromal compartment and within the tumor parenchyma are considered “hot”, while “cold” melanomas are characterized by a scarce immune infiltrate [ 117 , 118 ]. The use of PD-L1 expression alone to predict treatment response has shortcomings [ 119 ]. However, recent studies have shown that combining PD-L1 cell-type expression with tissue localization can have clinical implications [ 120 ].…”

Immunohistochemistry assessment of tissue neutrophil-to-lymphocyte ratio (tNLR) predicts outcomes in melanoma patients treated with anti-programmed cell death 1 therapy

“…The evaluation of immune cells in the tumor microenvironment is usually performed by conventional histopathology [hematoxylin and eosin (H&E) staining]. Immunohistochemistry (IHC), however, has gained prominence as a technique with greater sensitivity and specificity, enabling the proper differentiation of immune cells and the characterization of cell subtypes [19].…”