From Oncogenic Signaling Pathways to Single-Cell Sequencing of Immune Cells: Changing the Landscape of Cancer Immunotherapy

Abstract

Over the past decade, there have been remarkable advances in understanding the signaling pathways involved in cancer development. It is well-established that cancer is caused by the dysregulation of cellular pathways involved in proliferation, cell cycle, apoptosis, cell metabolism, migration, cell polarity, and differentiation. Besides, growing evidence indicates that extracellular matrix signaling, cell surface proteoglycans, and angiogenesis can contribute to cancer development. Given the genetic instability and vast intra-tumoral heterogeneity revealed by the single-cell sequencing of tumoral cells, the current approaches cannot eliminate the mutating cancer cells. Besides, the polyclonal expansion of tumor-infiltrated lymphocytes in response to tumoral neoantigens cannot elicit anti-tumoral immune responses due to the immunosuppressive tumor microenvironment. Nevertheless, the data from the single-cell sequencing of immune cells can provide valuable insights regarding the expression of inhibitory immune checkpoints/related signaling factors in immune cells, which can be used to select immune checkpoint inhibitors and adjust their dosage. Indeed, the integration of the data obtained from the single-cell sequencing of immune cells with immune checkpoint inhibitors can increase the response rate of immune checkpoint inhibitors, decrease the immune-related adverse events, and facilitate tumoral cell elimination. This study aims to review key pathways involved in tumor development and shed light on single-cell sequencing. It also intends to address the shortcomings of immune checkpoint inhibitors, i.e., their varied response rates among cancer patients and increased risk of autoimmunity development, via applying the data from the single-cell sequencing of immune cells.

A Systematic Review to Clarify the Prognostic Values of CD44 and CD44+CD24- Phenotype in Triple-Negative Breast Cancer Patients: Lessons Learned and The Road Ahead

“…Immunotherapeutic approaches are focused on stimulating anti-tumoral immune responses to reject tumoral cells. The PD-L1/programmed cell death protein 1 (PD-1) axis is a well-known inhibitory immune checkpoint axis that can substantially attenuate anti-tumoral immune responses ( 39 , 61 ). This axis can be established between tumoral cells and effector immune cells and shield the tumoral cells from anti-tumoral immune responses ( 40 ).…”

Analyzing Modern Biomolecules: The Revolution of Nucleic-Acid Sequencing – Review

“…That allows an unprecedented dissection of transcription within millions of individual cells. Both single-cell RNA sequencing (scRNA-seq) and single-nucleus RNA sequencing (snRNA-seq) have exciting applications [65][66][67][68][69][70][71][72][73][74][75][76][77], for instance: (i) discovering and characterizing cell type in health and diseases, such as cancer [13,[78][79][80][81][82][83][84][85][86][87][88][89], with implications in immunology [90], immune-mediated diseases [91], immunotherapy [92][93][94][95][96][97][98][99][100] and drug resistance [101]; (ii) deciphering the roles of such specific cell types in health and disease [102], including mitochondrial heteroplasmy [33]; and (iii) analyzing cell emergence, development and plasticity in tissues and organisms. These studies are also applied to study plant biology [103,104].…”

Immune Checkpoint Inhibitors in Colorectal Cancer: Challenges and Future Prospects

“…In order to overcome these obstacles, other therapeutic approaches and common therapies aiming to achieve better results are required. Among the new treatment options, immune checkpoint inhibitors (ICIs) are promising approaches in cancer therapy and have been successfully exploited for the treatment of melanoma, renal cell carcinoma (RCC), bladder cancer, lung cancer, and CRC [ 7 , 8 , 9 , 10 , 11 ].…”