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Cancer Stem Cells in Colorectal Cancer: Implications for Targeted Immunotherapies

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Abstract

Purpose

Colorectal cancers are composed of heterogeneous cell populations in the concepts of genetic and functional degrees that among them cancer stem cells are identified with their self-renewal and stemness capability mediating primary tumorigenesis, metastasize, therapeutic resistance, and tumor recurrence. Therefore, understanding the key mechanisms of stemness in colorectal cancer stem cells (CRCSCs) provides opportunities to discover new treatments or improve existing therapeutic regimens.

Methods

We review the biological significance of stemness and the results of potential CRCSC-based targeted immunotherapies. Then, we pointed out the barriers to targeting CRCSCs in vivo and highlight new strategies based on synthetic and biogenic nanocarriers for the development of future anti-CRCSC trials.

Results

The CSCs’ surface markers, antigens, neoantigens, and signaling pathways supportive CRCSCs or immune cells that are interacted with CRCSCs could be targeted by immune monotherapy or in formulation with developed nanocarriers to overcome the resistant mechanisms in immune evader CRCSCs.

Conclusion

Identification molecular and cellular cues supporting stemness in CRCSCs and their targeting by nanoimmunotherpy can improve the efficacy of existed therapies or explore novel therapeutic options in future.

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Abbreviations

ACT:

Improve adoptive cell therapy

CAR:

Chimeric antigen receptor

CRC:

Colorectal cancer

CRCSCs:

Colorectal cancer stem cells

EMT:

Epithelial-mesenchymal transition

ICD:

Immunogenic cell death

iPSC:

Induced pluripotent stem cell

mAb:

Monoclonal antibody

MDSCs:

Myeloid-derived suppressor cells

NP:

Nanoparticle

PD-1:

Programmed cell death 1

TAA:

Tumor-associated antigen

TIL:

Tumor infiltration lymphocyte

TMB:

Tumor mutational burden

TME:

Tumor microenvironment

Treg:

Regulatory T cell

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Authors and Affiliations

  1. Medical Laboratories Techniques Department, Al-Mustaqbal University College, Babylon, Hilla, 51001, Iraq

    Abduladheem Turki Jalil

  2. Department of Biochemistry, Faculty of Medicine, Anbar University, Anbar, Iraq

    Mohanad Ali Abdulhadi

  3. Department of Pharmaceutics Biomaterials, College of Pharmacy, Tehran University of Medical Science, Tehran, Iran

    Ahmed Mohsin Huran Al Jawadri

  4. College of Agriculture, National University of Science and Technology, Dhi Qar, Iraq

    Hayder Abdullah Talib

  5. Dentistry Department, Al-Turath University College, Baghdad, Iraq

    Abdul Kareem J. Al-Azzawi

  6. Medical Laboratory Technology Department, College of Medical Technology, The Islamic University, Najaf, Iraq

    Rahman S. Zabibah

  7. Medical Technical College, Al-Farahidi University, Baghdad, Iraq

    Ahmed Ali

Authors
  1. Abduladheem Turki Jalil
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  2. Mohanad Ali Abdulhadi
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  3. Ahmed Mohsin Huran Al Jawadri
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  4. Hayder Abdullah Talib
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  5. Abdul Kareem J. Al-Azzawi
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  6. Rahman S. Zabibah
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  7. Ahmed Ali
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Contributions

Abduladheem Turki Jalil: Conceptualization; investigation; writing, original draft; writing, review and editing; visualization; supervision; and project administration. Hayder Abdullah Talib, Rahman S. Zabibah, Ahmed Mohsin Huran Al Jawadri, Mohanad Ali Abdulhadi, Abdul Kareem J. Al-Azzawi, and Ahmed Ali: Investigation, writing — original draft. All co-authors approved the final version of the manuscript.

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Correspondence to Abduladheem Turki Jalil.

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Highlights

• CRCSCs provide tumor initiation, proliferation, metastasis, therapy resistance, and tumor recurrence.

• Characterization of the CRCSC-immune cell interaction contributes to the development of efficient therapeutic strategies.

• Allogenic or autologous immune cells are potent to eliminate CSCs with high-affinity targeting.

• Nano delivery systems provide simultaneous targeting of CRCSCs and tumor-supportive immune lineages.

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Jalil, A.T., Abdulhadi, M.A., Al Jawadri, A.M.H. et al. Cancer Stem Cells in Colorectal Cancer: Implications for Targeted Immunotherapies. J Gastrointest Canc 54, 1046–1057 (2023). https://doi.org/10.1007/s12029-023-00945-0

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  • DOI: https://doi.org/10.1007/s12029-023-00945-0

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