Milanckona Das, Amity University Kolkata
The desire to eliminate cancer permanently has remained an unattainable feat for scientists to this day. Although difficult to realize, it is a fact that our bodies continually deal with cancer on a minuscule level, daily. Immunotherapy is typically associated with cancer treatment, to effectively cause the cancellation of long-lasting cells. It aims at exploiting the adaptive and innate immune responses of the host. A molecular trail of origin written by any tumour is its language. Cancers are often the result of undesirable mutations caused by malformations in hereditary gene structures or may be caused by certain environmental or external factors like UV-radiation and cigarette smoke. Any of such disruptors may induce idiosyncratic changes in cellular DNA. That would in turn then lead to the scrambling of the DNA letter strand- a genetic orthography defect, which also, can cause cancer.
A complex network of Interactions caused by antagonistic cells might also create an impact on the immune system. The cells of the immune system consistently monitor every tissue across the body, regularly. Natural killer (NK) cells send stress associated molecules to damaged and cancerous cells. Dendritic cells activate cytotoxic T cells which can then send tumour associated antigens using their T cell receptor and co-receptors. However, several cancer cells remain undetected by our immune systems’ radar. Advanced sequencing methodologies and techniques now assist researchers in unravelling such complex issues for successfully delivering cures and treatments.
Cancer cells are the result of certain cellular mutations that cause them to divide unceasingly. The mutations often differ from patient to patient, even between neighbouring cancer cells, and this is due to the existence of different causes which give rise to the mutations. For researchers to be able to successfully establish effective therapies, it is pre-requisite for them to know how and which mutations are being alerted by the immune system and which are not. The production of abnormal or unstable proteins can be caused by carcinogenic cells. Proteins are continuously fragmented into peptides inside cells. Foreign peptides can be detected only if they appear on the cell surface. To bind peptides and translocate them to the cell surface, the immune system uses the Major Histocompatibility Complex (MHC) molecules. However, these differ considerably between all individuals and are not always able to bind the mutant peptides. Neoantigens are called mutant peptides that can activate an immune response and are tumour-specific. Researchers may use sequencing techniques to classify mutations based on the types of contributions made to neoantigens.
Comparing the DNA of a cancer cell to that of a healthy cell’s reveals cancer-causing mutations to a large extent. Then, RNA sequencing can be utilized to indicate the feasibility of generating anomalous proteins. Such sequencing can also reveal the appropriate MHC molecules would be necessary. This can then lead to the prediction of relevant neoantigen cells, along with mutant protein sequences. Although a thin possibility of the immune system to still miss and fail to react to the threat remains, even when the neoantigen complex of MHC has been formed.
T cells are how the body recognizes alien molecules. It would only be possible for spotting cancer neoantigen T cells with the right receptors. To design suitable immunotherapy, it is crucial to understand all these variations. Investigators may sequence or code the tumour invading T cells in such a manner that every strand is individually coded using cutting-edge techniques. Then this can reveal the number of cells that have the right receptor. And if a further search is conducted for the identification of their working genes, the cells fit to attack will also become visible.
One of the most complex biological interactions is between T cells, neoantigens and MHCs. But improved, faster and economical sequencing allows researchers to understand this entire process quickly and helps in assembling of the pieces of this complex puzzle. This knowledge is now helping to tailor therapies according to every individual patients’ immune system. Vaccines work by putting the body on high alert for a threat. A vaccine for cancer could boost the concentration of a tumour’s neoantigens, switching on the immune system. It will then speed up the immune system’s battle against a tumour by overwhelming the tumour with appropriate T cells.
Such immunotherapeutic triumphs enable scientists to envision and improve upon the existing methodologies, maintaining the success of science in the long-running battle of mankind and cancer.
Also read: Serotonin promotes patience- a new therapy
Reference:Sprooten, J., Ceusters, J., Coosemans, A., Agostinis, P., De Vleeschouwer, S., Zitvogel, L., Kroemer, G., Galluzzi, L., & Garg, A. D. (2019). Trial watch: Dendritic cell vaccination for cancer immunotherapy. OncoImmunology, 8(11), 1638212. https://doi.org/10.1080/2162402X.2019.1638212
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