Recent progress in cancer immunotherapy: Overview of current status and challenges.

Cancer treatment is presently one of the most important challenges in medical science. Surgery, chemotherapy, radiotherapy, or combining these methods is used to eliminate the tumor. Hormone therapy, bone marrow transplantation, stem cell therapy as well as immunotherapy are other well-known therapeutic modalities. Immunotherapy, as the most important complementary method, uses the immune system for treating cancer followed by surgery, chemotherapy, and radiotherapy. This method is systematically used to prevent malignancies development mainly via potentiating antitumor immune cells activation and conversely compromising their exhaustion with the lowest negative effects on healthy cells. Active immunotherapy can be employed for cancer immunotherapy by directly using the ingredients of the immune system and activating immune responses. On the other hand, inactive immunotherapy is utilized by indirect induction and using immune cell-based products consisting of monoclonal antibodies. It has strongly been proved that combination therapy with immunotherapies and other therapeutic means, such as anti-angiogenic agents, could be a rational plan to treat cancer. Herein, we have focused on recent findings concerning the therapeutic merits of cancer therapy using immune checkpoint inhibitors (ICIs), adoptive cell transfer (ACT) and cancer vaccine alone or in combination with other approaches. Also, we offer a glimpse into the current challenges in this context.

The role of the natural killer (NK) cell modulation in breast cancer incidence and progress.

The importance of the immune system on tumor surveillance has been investigated for many years, and its impact on controlling tumor progression has been verified. An important subgroup of the innate immune system is natural killer (NK) cells, whose essential function in modulating tumor behavior and suppressing metastasis and tumor growth has been demonstrated. The first idea of NK cells' crucial biological processes was demonstrated through their potent ability to conduct direct cellular cytotoxicity, even without former sensitization. These properties of NK cells allow them to recognize transformed cells that have attenuated self-ligand and express stress-induced ligands. Furthermore, secretion of various cytokines and chemokines after their activation leads to tumor elimination via either direct cytotoxic effect on malignant cells or activation of the adaptive immune system. In addition, novel immunotherapeutic approaches tend to take advantage of NK cells' ability, leading to antibody-based approaches, the formation of engineered CAR-NK cells, and adoptive cell transfer. However, the restricted functionality of NK cells and the inability to infiltrate tumors are its blind spots in breast cancer patients. In this review, we gathered newly acquired data on the biology and functions of NK cells in breast cancer and proposed ways to employ this knowledge for novel therapeutic approaches in cancers, particularly breast cancer.

Metallic Nanoparticles for the Modulation of Tumor Microenvironment; A New Horizon.

Cancer is one of the most critical human challenges which endangers many people's lives every year with enormous direct and indirect costs worldwide. Unfortunately, despite many advanced treatments used in cancer clinics today, the treatments are deficiently encumbered with many side effects often encountered by clinicians while deploying general methods such as chemotherapy, radiotherapy, surgery, or a combination thereof. Due to their low clinical efficacy, numerous side effects, higher economic costs, and relatively poor acceptance by patients, researchers are striving to find better alternatives for treating this life-threatening complication. As a result, Metal nanoparticles (Metal NPs) have been developed for nearly 2 decades due to their important therapeutic properties. Nanoparticles are quite close in size to biological molecules and can easily penetrate into the cell, so one of the goals of nanotechnology is to mount molecules and drugs on nanoparticles and transfer them to the cell. These NPs are effective as multifunctional nanoplatforms for cancer treatment. They have an advantage over routine drugs in delivering anticancer drugs to a specific location. However, targeting cancer sites while performing anti-cancer treatment can be effective in improving the disease and reducing its complications. Among these, the usage of these nanoparticles (NPs) in photodynamic therapy and sonodynamic therapy are notable. Herein, this review is aimed at investigating the effect and appliances of Metal NPs in the modulation tumor microenvironment which bodes well for the utilization of vast and emerging nanomaterial resources.

Role of hypothalamic-pituitary adrenal-axis, toll-like receptors, and macrophage polarization in pre-atherosclerotic changes induced by social isolation stress in mice.

It has been well documented that chronic stress can induce atherosclerotic changes, however, the underlying mechanisms is yet to be established. In this regard, this study aimed to elucidate the relation between hypothalamic-pituitary adrenal-axis (HPA-axis), toll-like receptors (TLRs), as well as M1/M2 macrophage ratio and pre-atherosclerotic changes in social isolation stress (SIS) in mice. We used small interfering RNA against the glucocorticoid receptor (GR) to evaluate the relation between HPA-axis and TLRs. C57BL/6J mice were subjected to SIS and RT-PCR, ELISA, flow cytometry, and immunohistochemistry were used to assess the relations between pre-atherosclerotic changes and TLRs, macrophage polarization, pro-inflammatory cytokines, and cell adhesion molecules in aortic tissue. We used TAK-242 (0.3 mg/kg, intraperitoneally), a selective antagonist of TLR4, as a possible prophylactic treatment for atherosclerotic changes induced by SIS. We observed that isolated animals had higher serum concentration of corticosterone and higher body weight in comparison to normal animals. In isolated animals, results of in vitro study showed that knocking-down of the GR in bone marrow-derived monocytes significantly decreased the expression of TLR4. In vivo study suggested higher expression of TLR4 on circulating monocytes and higher M1/M2 ratio in aortic samples. Pathological study showed a mild pre-atherosclerotic change in isolated animals. Finally, we observed that treating animals with TAK-242 could significantly inhibit the pre-atherosclerotic changes. SIS can possibly increase the risk of atherosclerosis through inducing abnormal HPA-axis activity and subsequently lead to TLR4 up-regulation, vascular inflammation, high M1/M2 ratio in intima. Thus, TLR4 inhibitors might be a novel treatment to decrease the risk of atherosclerosis induced by chronic stress.