Single-Cell Transcriptomics for Unlocking Personalized Cancer Immunotherapy: Toward Targeting the Origin of Tumor Development Immunogenicity

SIMPLE SUMMARY: This study explains how the application of single-cell transcriptomics can enhance personalized cancer immunotherapy. Tumors exhibit complex and heterogeneous characteristics that can impede the effectiveness of immunotherapy. We specifically present the “Origin of Tumor Development” (OTD), consisting of undifferentiated tumor cells, which contribute to tumor diversity and heterogeneity. Using single-cell transcriptomics, scientists can analyze the gene expression profiles of individual tumor cells to gain insight into tumorigenesis, progression, and immune evasion. This approach enables the identification of personalized biomarkers and targets, including immune checkpoints and tumor-infiltrating lymphocytes, tailored to each patient. We also discuss future directions, such as the development of analytical tools and databases, to maximize the potential for targeting the patient’s OTD cells and advance personalized cancer immunotherapy. ABSTRACT: Cancer immunotherapy is a promising approach for treating malignancies through the activation of anti-tumor immunity. However, the effectiveness and safety of immunotherapy can be limited by tumor complexity and heterogeneity, caused by the diverse molecular and cellular features of tumors and their microenvironments. Undifferentiated tumor cell niches, which we refer to as the “Origin of Tumor Development” (OTD) cellular population, are believed to be the source of these variations and cellular heterogeneity. From our perspective, the existence of distinct features within the OTD is expected to play a significant role in shaping the unique tumor characteristics observed in each patient. Single-cell transcriptomics is a high-resolution and high-throughput technique that provides insights into the genetic signatures of individual tumor cells, revealing mechanisms of tumor development, progression, and immune evasion. In this review, we explain how single-cell transcriptomics can be used to develop personalized cancer immunotherapy by identifying potential biomarkers and targets specific to each patient, such as immune checkpoint and tumor-infiltrating lymphocyte function, for targeting the OTD. Furthermore, in addition to offering a possible workflow, we discuss the future directions of, and perspectives on, single-cell transcriptomics, such as the development of powerful analytical tools and databases, that will aid in unlocking personalized cancer immunotherapy through the targeting of the patient’s cellular OTD.