Single-Cell Analysis in Immuno-Oncology

Abstract

The complexity of the cellular and non-cellular milieu surrounding human tumors plays a decisive role in the course and outcome of disease. The high variability in the distribution of the immune and non-immune compartments within the tumor microenvironments (TME) among different patients governs the mode of their response or resistance to current immunotherapeutic approaches. Through deciphering this diversity, one can tailor patients’ management to meet an individual’s needs. Single-cell (sc) omics technologies have given a great boost towards this direction. This review gathers recent data about how multi-omics profiling, including the utilization of single-cell RNA sequencing (scRNA-seq), assay for transposase-accessible chromatin with sequencing (scATAC-seq), T-cell receptor sequencing (scTCR-seq), mass, tissue-based, or microfluidics cytometry, and related bioinformatics tools, contributes to the high-throughput assessment of a large number of analytes at single-cell resolution. Unravelling the exact TCR clonotype of the infiltrating T cells or pinpointing the classical or novel immune checkpoints across various cell subsets of the TME provide a boost to our comprehension of adaptive immune responses, their antigen specificity and dynamics, and grant suggestions for possible therapeutic targets. Future steps are expected to merge high-dimensional data with tissue localization data, which can serve the investigation of novel multi-modal biomarkers for the selection and/or monitoring of the optimal treatment from the current anti-cancer immunotherapeutic armamentarium.

Advancing immunotherapy for melanoma: the critical role of single-cell analysis in identifying predictive biomarkers

“…Moreover, scRNA-seq facilitates the discovery of novel biomarkers beyond traditional approaches. For instance, circulating tumor cells (CTCs) and immune cells in the bloodstream harbor valuable information reflecting tumor dynamics and therapy response ( 74 , 75 ). Recent studies have identified specific cell subsets, such as B cell clones and monocyte phenotypes, associated with improved survival and therapy response in melanoma patients undergoing ICI treatment ( 76 ).…”

Unveiling the Immune Microenvironment’s Role in Breast Cancer: A Glimpse into Promising Frontiers

“…Furthermore, tailoring immunotherapeutic strategies for BC management involves developing patient-specific approaches [25]. This is achieved by taking into account individual immune profiles, genomic alterations, and tumor characteristics [257]. Moreover, investigating the mechanisms behind resistance that may develop in response to immunotherapy is essential.…”

Harnessing the Transcriptional Signatures of CAR-T-Cells and Leukemia/Lymphoma Using Single-Cell Sequencing Technologies

“…While traditional techniques allow for the quantitative profiling of genomic, transcriptomic, and proteomic signatures in bulk tumors, the advent of single-cell sequencing has catalyzed significant advancements in identifying innovative biomarkers, novel cellular phenotypes, and new therapeutic targets that remain undetectable through bulk-sequencing approaches [43][44][45] (Figure 1A). Despite a limited sensitivity to detect low-abundance RNAs and "technical noise" due to the low amount of input material [46,47], single-cell sequencing, with its high resolution, serves as an invaluable tool for studying the properties of immune cells. This includes exploring diverse developmental lineages, antigen specificity, phenotypic plasticity, cellular transitions, interactions, cellular communications, and adaptability to various microenvironments [45,[48][49][50][51][52][53][54][55][56].…”