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Dendritic cells: The awakening of your immune system

What are the dendritic cells? Dendritic cells are phagocytes, a special type of immune cell found in tissues, such as the skin, which stimulate immune responses by presenting an antigen on its surface earlier than other cells of the immune system.

The idea that the immune system has anti-cancer capabilities is not new. At the beginning of the 20th century, Paul Ehrlich proposed his theory of immunological surveillance for cancer. [1] According to Ehrlich, the tumor cells appeared spontaneously in the body and the immune system eliminated them. In fact, it seems that the efficacy of classical treatments also largely depends on the activation of immunological responses after the release of immuno-stimulatory molecules from necrotic cells.

The efficacy of immunotherapy against cancer depends on the immunogenicity of tumor cells to induce cytotoxic T responses. [2] Therefore, cancer cells should express immunogenic antigens that can become therapeutic targets. The first immunotherapies, available in the 60s, were directed against viral antigens expressed by oncogenic viruses.

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However, only a low number of human cancers are caused by viral infections. In fact, the theory of the viral etiology of cancers could not explain the immunological responses generated against chemically induced tumors or the spontaneous regressions of cancers in people vaccinated against common pathogens or by administering adjuvants. These results demonstrated the existence of tumor antigens of non-viral origin. [3]

With the passage of time, it was discovered that cancer cells accumulated transformative mutations that resulted in genetic instability, increased cell survival, and uncontrolled proliferation. Many of the proteins affected in these mutations are transcription factors, intracellular signaling molecules (ras), cell division regulators and anti-oncogenes. The uncontrolled proliferation and the defects in the cellular DNA repair provoke even more mutations, which give rise to the aberrant expression of cellular proteins (mutated or not), conferring immunogenicity to the cancer cells. [4]

Immunotherapy against cancer with dendritic cells

Dendritic cells are the most effective and ideal antigen presenting cells for immunotherapy. Dendritic cells are easily differentiated from mouse bone marrow using recombinant GM-CSF, and also from human monocytes. These ex vivo production methods accelerated the progress of DC-based immunotherapy, as their number ceased to be a limiting factor.

Differentiated dendritic cells are phenotypically and functionally immature, which facilitates their manipulation. One of the great problems of immunotherapy against cancer, however, is the inefficient activation of effector T cells. Thus, vaccination with Dendritic cells seems to be the best option. The enhancement of their endogenous antigen presentation capabilities could break the natural tolerance against endogenous tumor antigens. [5]

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The large-scale production of dendritic cells allowed its direct application in vaccination, after incubation with tumor antigens, either in the form of peptides or from tumor lysates. Another advantage of the ex vivo production of dendritic cells is the ease with which they can be genetically modified with viral and non-viral vectors. In addition, since its state of maturation can be controlled with relative ease, dendritic cells are ideal for immunotherapies.

Dendritic cells generated ex vivo have been used to generate T responses against infectious agents and cancer. The preclinical results in immunotherapy with DC-generated ex vivo have provided relevant data tools. [6]

No question, this field of research opens up an exciting and encouraging new horizon of cancer therapies and is something our patients at Verita Life already benefit from.

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References

  1. Domenico Ribatti. The concept of immune surveillance against tumors: The first theories Oncotarget. 2017 Jan 24; 8(4): 7175–7180. Published online 2016 Oct 18. doi: 10.18632/oncotarget.12739, PMCID: PMC5351698, PMID: 27764780
  2. Christina M. Celluzzi and Louis D. Falo, Jr, Cutting Edge: Physical Interaction Between Dendritic Cells and Tumor Cells Results in an Immunogen That Induces Protective and Therapeutic Tumor Rejection, https://www.researchgate.net/profile/Christina_Celluzzi/publication/51323691_Cutting_Edge_Physical_Interaction_Between_Dendritic_Cells_and_Tumor_Cells_Results_in_an_Immunogen_That_Induces_Protective_and_Therapeutic_Tumor_Rejection1/links/00b7d526a7b855b349000000.pdf
  3. Barry R. Blakley, Journal of Applied Toxicology, Volume 6, Issue 6, December 1986, Pages 425-429, The effect of cadmium on chemical‐ and viral‐induced tumor production in mice. First published: December 1986 https://doi.org/10.1002/jat.2550060608
  4. Sajib Chakraborty and Taibur Rahman, The difficulties in cancer treatment, Ecancermedicalscience. 2012; 6: ed16. Published online 2012 Nov 14. doi: 10.3332/ecancer.2012.ed16, PMCID: PMC4024849, PMID: 24883085,
  5. Rachel Lubong Sabado and Nina Bhardwaj, Directing dendritic cell immunotherapy towards successful cancer treatment, Immunotherapy. 2010 Jan 1; 2(1): 37–56. doi: 10.2217/imt.09.43 PMCID: PMC2867472 NIHMSID: NIHMS171812 PMID: 20473346
  6. Eli Gilboa, DC-based cancer vaccines, J Clin Invest. 2007 May 1; 117(5): 1195–1203. Published online 2007 May 1. doi: 10.1172/JCI31205 PMCID: PMC1857263 PMID: 17476349