Current Technologies and Future Perspectives in Immunotherapy towards a Clinical Oncology Approach.

Immunotherapy is now established as a potent therapeutic paradigm engendering antitumor immune response against a wide range of malignancies and other diseases by modulating the immune system either through the stimulation or suppression of immune components such as CD4+ T cells, CD8+ T cells, B cells, monocytes, macrophages, dendritic cells, and natural killer cells. By targeting several immune checkpoint inhibitors or blockers (e.g., PD-1, PD-L1, PD-L2, CTLA-4, LAG3, and TIM-3) expressed on the surface of immune cells, several monoclonal antibodies and polyclonal antibodies have been developed and already translated clinically. In addition, natural killer cell-based, dendritic cell-based, and CAR T cell therapies have been also shown to be promising and effective immunotherapeutic approaches. In particular, CAR T cell therapy has benefited from advancements in CRISPR-Cas9 genome editing technology, allowing the generation of several modified CAR T cells with enhanced antitumor immunity. However, the emerging SARS-CoV-2 infection could hijack a patient's immune system by releasing pro-inflammatory interleukins and cytokines such as IL-1ß, IL-2, IL-6, and IL-10, and IFN-γ and TNF-α, respectively, which can further promote neutrophil extravasation and the vasodilation of blood vessels. Despite the significant development of advanced immunotherapeutic technologies, after a certain period of treatment, cancer relapses due to the development of resistance to immunotherapy. Resistance may be primary (where tumor cells do not respond to the treatment), or secondary or acquired immune resistance (where tumor cells develop resistance gradually to ICIs therapy). In this context, this review aims to address the existing immunotherapeutic technologies against cancer and the resistance mechanisms against immunotherapeutic drugs, and explain the impact of COVID-19 on cancer treatment. In addition, we will discuss what will be the future implementation of these strategies against cancer drug resistance. Finally, we will emphasize the practical steps to lay the groundwork for enlightened policy for intervention and resource allocation to care for cancer patients.

Impacts of gut microbiota alteration on age-related chronic liver diseases.

The gut microbiome and its metabolites are involved in developing and progressing liver disease. Various liver illnesses, such as non-alcoholic fatty liver disease, alcoholic liver disease, hepatitis C, and hepatocellular carcinoma, are made worse and have worse prognoses with aging. Dysbiosis, which occurs when the symbiosis between the microbiota and the host is disrupted, can significantly negatively impact health. Liver disease is linked to qualitative changes, such as an increase in hazardous bacteria and a decrease in good bacteria, as well as quantitative changes in the overall amount of bacteria (overgrowth). Intestinal gut microbiota and their metabolites may lead to chronic liver disease development through various mechanisms, such as increasing gut permeability, persistent systemic inflammation, production of SCFA, bile acids, and alteration in metabolism. Age-related gut dysbiosis can disrupt the communication between gut microbiota and the host, impacting the host's health and lifespan. With aging, a gradual loss of the ability to maintain homeostasis because of structural alteration and gut dysbiosis leads to the disease progression in end-stage liver disease. Recently chronic liver disease has been identified as a global problem. A large number of patients are receiving liver transplants yearly. Thereby gut microbiome ecology is changing in the patients of the gut due to the changes in pathophysiology during the preoperative stage. The present review summarises the age-associated dysbiosis of gut microbial composition and its contribution to chronic liver disease. This review also provides information about the impact of liver transplant on the gut microbiome and possible disadvantageous effects of alteration in gut microbiota.

Plant-derived bioactive compounds in colon cancer treatment: An updated review.

Colon cancer is the third most predominant cancer caused by genetic, environmental and nutritional factors. Plant-based compounds are very well known to regress colon cancer in many ways, like delaying tumor growth, managing chemotherapy and radiation therapy side-effects, and working at the molecular levels. Medicinal plants contain many bioactive phytochemicals such as flavonoids, polyphenol compounds, caffeic acid, catechins, saponins, polysaccharides, triterpenoids, alkaloids, glycosides, phenols, quercetin, luteolin, kaempferol and luteolin glycosides, carnosic acid, oleanolic acid, rosmarinic acid, emodin, and eugenol and anthricin. These bioactive compounds can reduce tumor cell proliferation via several mechanisms, such as blocking cell cycle checkpoints and promoting apoptosis through activating initiator and executioner caspase. Traditional medicines have been used globally to treat cancers because of their anti-cancer effects, antioxidant properties, anti-inflammatory properties, anti-mutagenic effects, and anti-angiogenic effects. In addition, these medicines effectively suppress early and intermediate stages of carcinogenesis when administered in their active and pure form. However, traditional medicine is not very popular due to some critical challenges. These include poor solubility and absorption of these compounds, intellectual property-related issues, involvement of drug synergism, absence of drug-likeness, and unsure protocols for their extraction from the plant source. Using bioactive compounds in colon cancer has equal advantages and limitations. This review highlights the benefits and challenges of using bioactive compounds derived from plants for colon cancer. We have also discussed using these compounds to target cancer stem cell self-renewal, its effects on cancer cell metabolism, safety parameters, easy modulation, and their bioavailability.