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Review

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

by
Afshin Derakhshani
1,2,†,
Zeinab Rostami
3,
Hossein Safarpour
4,†,
Mahdi Abdoli Shadbad
1,5,†,
Niloufar Sadat Nourbakhsh
6,
Antonella Argentiero
2,*,
Sina Taefehshokr
1,
Neda Jalili Tabrizi
1,
Omid Kooshkaki
3,
Reza Vaezi Astamal
1,
Pankaj Kumar Singh
7,
Nima Taefehshokr
8,
Nazila Alizadeh
1,
Nicola Silvestris
2,9,‡ and
Behzad Baradaran
1,10,*,‡
1
Immunology Research Center, Tabriz University of Medical Sciences, Tabriz 51656-65811, Iran
2
IRCCS Istituto Tumori “Giovanni Paolo II” of Bari, 70124 Bari, Italy
3
Student Research Committee, Birjand University of Medical Sciences, Birjand 97178-53577, Iran
4
Cellular & Molecular Research Center, Birjand University of Medical Sciences, Birjand 97178-53577, Iran
5
Student Research Committee, Tabriz University of Medical Sciences, Tabriz 51666-14766, Iran
6
Department of Biology, Islamic Azad University, Varamin-Pishva Branch, Tehran 33817-74895, Iran
7
Principal Research Technologist, Department of Radiation Oncology, Mayo Clinic, 4500 San Pablo Rd S, Jacksonville, FL 32224, USA
8
Department of Microbiology and Immunology, Center for Human Immunology, The University of Western Ontario, London, ON N6A 5C1, Canada
9
Department of Biomedical Sciences and Human Oncology, University of Bari “Aldo Moro”, 70124 Bari, Italy
10
Department of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz 51666-14766, Iran
*
Authors to whom correspondence should be addressed.
†
These authors contributed equally to this manuscript.
‡
These authors contributed equally to this manuscript.
Molecules 2021, 26(8), 2278; https://doi.org/10.3390/molecules26082278
Submission received: 22 January 2021 / Revised: 9 April 2021 / Accepted: 9 April 2021 / Published: 14 April 2021
(This article belongs to the Special Issue The Future of the Cancer Treatment: The Immunotherapy Next Generation)
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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.
Keywords: cancer; tumor microenvironment; signaling pathways; single-cell omics; tumor-infiltrating immune cells; single-cell sequencing of immune cells; immune checkpoints cancer; tumor microenvironment; signaling pathways; single-cell omics; tumor-infiltrating immune cells; single-cell sequencing of immune cells; immune checkpoints

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MDPI and ACS Style

Derakhshani, A.; Rostami, Z.; Safarpour, H.; Shadbad, M.A.; Nourbakhsh, N.S.; Argentiero, A.; Taefehshokr, S.; Tabrizi, N.J.; Kooshkaki, O.; Astamal, R.V.; et al. From Oncogenic Signaling Pathways to Single-Cell Sequencing of Immune Cells: Changing the Landscape of Cancer Immunotherapy. Molecules 2021, 26, 2278. https://doi.org/10.3390/molecules26082278

AMA Style

Derakhshani A, Rostami Z, Safarpour H, Shadbad MA, Nourbakhsh NS, Argentiero A, Taefehshokr S, Tabrizi NJ, Kooshkaki O, Astamal RV, et al. From Oncogenic Signaling Pathways to Single-Cell Sequencing of Immune Cells: Changing the Landscape of Cancer Immunotherapy. Molecules. 2021; 26(8):2278. https://doi.org/10.3390/molecules26082278

Chicago/Turabian Style

Derakhshani, Afshin, Zeinab Rostami, Hossein Safarpour, Mahdi Abdoli Shadbad, Niloufar Sadat Nourbakhsh, Antonella Argentiero, Sina Taefehshokr, Neda Jalili Tabrizi, Omid Kooshkaki, Reza Vaezi Astamal, and et al. 2021. "From Oncogenic Signaling Pathways to Single-Cell Sequencing of Immune Cells: Changing the Landscape of Cancer Immunotherapy" Molecules 26, no. 8: 2278. https://doi.org/10.3390/molecules26082278

APA Style

Derakhshani, A., Rostami, Z., Safarpour, H., Shadbad, M. A., Nourbakhsh, N. S., Argentiero, A., Taefehshokr, S., Tabrizi, N. J., Kooshkaki, O., Astamal, R. V., Singh, P. K., Taefehshokr, N., Alizadeh, N., Silvestris, N., & Baradaran, B. (2021). From Oncogenic Signaling Pathways to Single-Cell Sequencing of Immune Cells: Changing the Landscape of Cancer Immunotherapy. Molecules, 26(8), 2278. https://doi.org/10.3390/molecules26082278

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