Immune Checkpoint Regulators: A New Era Toward Promising Cancer Therapy

Abstract

<jats:sec> <jats:title /> <jats:p>During the last century, our battle against cancer has been inaugurated upon three main approaches; surgery, radiation and chemotherapy. The latest findings on the effectiveness of immunotherapy in cancer management offer a ray of hope after decades of research and studies on the best treatment methods. Immunotherapy has proven effective in the surveillance and destruction of cancer- causing cells, demonstrating its ability to suppress cancer through controlling the wellestablished immune-editing process. Immuno-editing is a process that comprises three principal elements; elimination, equilibrium, and escape, and is paramount to the comprehension of checkpoint inhibition. Cancer cells employ various approaches to evade the elimination step leading to its immune- escape. The escape mechanism encompasses the up-regulation of negative co-signals that block successful activation of cancer-eradicating immune cells, developing cytokine background that favors the immunosuppressive tumor microenvironment (TME), or dropping the expression of tumor- specific proteins known as neo-antigens, therefore reducing the immunogenic activity against cancer cells. Today, checkpoint inhibitors are considered as a primary approach in our fight against cancer. Strategies targeting the inhibitory roles of checkpoint inhibitors have been shown effective against different cancer types and stages, and some already gained the FDA’s approval. This review seeks to comprehensively cover the historical background as well as the most recent updates for the role of immune checkpoint regulators in the maintenance of immune homeostatic balance as well as keeping the tumorigenic cells in check.</jats:p> </jats:sec>

Vaccines in Breast Cancer: Challenges and Breakthroughs

“…However, it results in the formation of cancer cells with decreased immunogenicity, epigenetic alterations, and genetic instability [ 117 ], thus making them capable of escaping the immune detection and destruction [ 118 ]. Such cells that escape the immunological pressure finally enter the third stage of immunoediting, where the immune system barely puts any restraints on the progression of the modified tumour cells as in Figure 1 [ 119 ].…”

Untousling the Role of Tousled-like Kinase 1 in DNA Damage Repair

“…Moreover, TLK2 depletion culminates in a BLM-dependent, STING-mediated innate immune response, whereby, in many human cancers, TLK1/2 expression correlates with signatures of chromosomal instability and anti-correlates with STING and innate and adaptive immune response signatures [45]. All this prompts an exciting but challenging new prospective view of how TLKs may operate in terms of different, albeit still understudied, aspects of their involvement in cancer development and progression and as a possible target in cancer immunotherapy and maybe in immune checkpoint regulation [58,59], recombination, and cytokine signaling [5]. Further important genetic evidence came from the identification of a novel heterozygous variant of TLK1 in a patient with a neuro-developmental and immunological syndrome.…”

COVID-19 and the Immune Response: A Multi-Phasic Approach to the Treatment of COVID-19

“…This is similar to the way cancerous cells and other viruses such as human immunodeficiency virus (HIV) cause mortality by triggering overactivity and subsequent exhaustion of the host immune system. Immune checkpoints are points in the cycle of immune regulation that are influencable primarily by cell-surface regulators [ 75 ]. For example, deficiency in the P-selectin glycoprotein ligand-1 (PSGL-1) adhesion molecule has been correlated with better T cell survival and improved viral clearance in mice [ 76 ].…”