Cancer the neoantigen formed by the cancer cells as

Cancer
is a chronic disease whose emergence and advancement is still mysterious to
many scientists. There are multiple rationales for the development of the
disease such as epigenetic factors, mutations in the gene, an impaired host
immune system and many more. 1 Hence, cancer is the irregular production
of a cell caused due to epigenetics and genetic factors. 2 For the
treatment of cancer, researchers have been focusing on the hallmarks of
cancers. 3 The hallmarks of cancer are angiogenesis, enabling
replicative immorality, sustaining signals for proliferation, deterring cell
death, evading immune surveillance and triggering invasion and metastasis.
2 Presently, the focal point of numerous experiments is to understand
two hallmarks: the spread of cancer from a primary site to other tissues and escaping
of cancer cells from the immune surveillance. 3 Metastasis of
cancer is accomplished due to various reasons including the genome metastasis
hypothesis. Our laboratory is working on genome metastasis; the theory explains that cell free
chromatin from cancer cells acts as a seeds for the formation of supportive metastatic
niche formation into distant organs (soil). When the cancer patients undergo
chemotherapy or radiation, a vast number of cells die. From the dead cell, the
chromatin fragments are released into circulation and these fragments can
thereby, integrate into the normal DNA of other cells inducing genome instability.
4

 

The
immune system recognises the neoantigen formed by the cancer cells as foreign
and elicit an immune response by triggering the T cells which eventually initiates
the production of cytotoxic T lymphocytes (CTLs). 5 To induce an
immunogenic response it is essential to have the co-stimulatory signals and coordination
of CTLs. 56 Under normal physiology, T cells are constantly
under the regulatory control by Tregs (CD4+, CD25+, FOXP3+) as a part of
peripheral tolerance, including the checkpoints Programmed Death 1 (PD1) to
avoid damage to the host. 7 Cancer cells antigens establish
tolerance against the T cells MHC repertoire by exploiting the PD1 pathway for
its own growth and development. PD1 is expressed on variety of immune cells
including T cells, B cells, dendritic cells and tumour infiltrating
lymphocytes. PD1 has two ligands, PDL1 and PDL2. PDL1 is present on tumour
cells and antigen presenting cells. Its role in cancer is very prominent. There
is minimal information on PDL2 and yet no relationship has been deduced to
cancer. 8 PDL1 is produced on cancer cells due to its
microenvironment, the over secretion of pro inflammatory cytokines of tumour
necrosis factor alpha and interferon gamma. When PD1 on the immune cells bind
to the PDL1 on tumour cell it results in the T cell exhaustion, conversion of
naïve CD4+ T cells to Treg cells eventually diminishing immune response.910
The goal of this study is to therefore understand if PD1 expression is caused
and modulated by cancer cell free chromatin. Future, the proposal aims to
inhibit cancer cfCh and analyse the expression of PD1. 

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