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

Afshin Derakhshani, Zeinab Rostami, Hossein Safarpour, Mahdi Abdoli Shadbad, Niloufar Sadat Nourbakhsh, Antonella Argentiero, Sina Taefehshokr, Neda Jalili Tabrizi, Omid Kooshkaki, Reza Vaezi Astamal, Pankaj Kumar Singh, Nima Taefehshokr, Nazila Alizadeh, Nicola Silvestris, Behzad Baradaran

Research output: Contribution to journalReview articlepeer-review


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.

Original languageEnglish
Article number2278
JournalMolecules (Basel, Switzerland)
Issue number8
Publication statusPublished - Apr 14 2021


  • cancer
  • immune checkpoints
  • signaling pathways
  • single-cell omics
  • single-cell sequencing of immune cells
  • tumor microenvironment
  • tumor-infiltrating immune cells

ASJC Scopus subject areas

  • Analytical Chemistry
  • Chemistry (miscellaneous)
  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery
  • Physical and Theoretical Chemistry
  • Organic Chemistry


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