Immunotherapy, especially immune checkpoint blockade therapy, represents a major milestone in the history of cancer therapy. However, the current response rate to immunotherapy among cancer patients must be improved; thus, new strategies for sensitizing patients to immunotherapy are urgently needed. Erythroid progenitor cells (EPCs), a population of immature erythroid cells, exert potent immunosuppressive functions. As a newly recognized immunosuppressive population, EPCs have not yet been effectively targeted. In this review, we summarize the immunoregulatory mechanisms of EPCs, especially for CD45+ EPCs. Moreover, in view of the regulatory effects of EPCs on the tumor microenvironment, we propose the concept of EPC-immunity, present existing strategies for targeting EPCs, and discuss the challenges encountered in both basic research and clinical applications. In particular, the impact of existing cancer treatments on EPCs is discussed, laying the foundation for combination therapies. The aim of this review is to provide new avenues for improving the efficacy of cancer immunotherapy by targeting EPCs.

Millions of people worldwide are affected by leishmaniasis, caused by the Leishmania parasite. Effective treatment is challenging due to the biological complexity of the parasite, drug toxicity, and increasing resistance to conventional drugs. To combat this disease, the development of specific strategies to target and selectively eliminate the parasite is crucial. This Review highlights the importance of amino acids in the developmental stages of Leishmania as a factor determining whether the infection progresses or is suppressed. It also explores the use of peptides as alternatives in parasite control and the development of novel targeted treatments. While these strategies show promise for more effective and targeted treatment, further studies to address the remaining challenges are imperative.

Colitis-associated colorectal cancer has been a hot topic in public health issues worldwide. Numerous studies have demonstrated the significance of myeloid-derived suppressor cells (MDSCs) in the progression of this ailment, but the specific mechanism of their role in the transformation of inflammation to cancer is unclear, and potential therapies targeting MDSC are also unclear. This paper outlines the possible involvement of MDSC to the development of colitis-associated colorectal cancer. It also explores the immune and other relevant roles played by MDSC, and collates relevant targeted therapies against MDSC. In addition, current targeted therapies for colorectal cancer are analyzed and summarized.

The intriguing scientific relationship between autoimmunity and cancer immunology have been traditionally indulged to throw spotlight on novel pathological targets. Understandably, these \"slowly killing\" diseases are on the opposite ends of the immune spectrum. However, the immune regulatory mechanisms between autoimmunity and cancer are not always contradictory and sometimes mirror each other based on disease stage, location, and timepoint. Moreover, the blockade of immune checkpoint molecules or signalling pathways that unleashes the immune response against cancer is being leveraged to preserve self-tolerance and treat many autoimmune disorders. Therefore, understanding the common crucial factors involved in cancer is of paramount importance to paint the autoimmune disease spectrum and validate novel drug candidates. In the current review, we will broadly describe how ZEB1, or Zinc-finger E-box Binding Homeobox 1, reinforces immune exhaustion in cancer or contributes to loss of self-tolerance in auto-immune conditions. We made an effort to exchange information about the molecular pathways and pathological responses (immune regulation, cell proliferation, senescence, autophagy, hypoxia, and circadian rhythm) that can be regulated by ZEB1 in the context of autoimmunity. This will help untwine the intricate and closely postured pathogenesis of ZEB1, that is less explored from the perspective of autoimmunity than its counterpart, cancer. This review will further consider several approaches for targeting ZEB1 in autoimmunity.

RNA-based therapeutics have shown great promise in various medical applications, including cancers, infectious diseases, and metabolic diseases. The recent success of mRNA vaccines for combating the COVID-19 pandemic has highlighted the medical value of RNA drugs. However, one of the major challenges in realizing the full potential of RNA drugs is to deliver RNA into specific organs and tissues in a targeted manner, which is crucial for achieving therapeutic efficacy, reducing side effects, and enhancing overall treatment efficacy. Numerous attempts have been made to pursue targeting, nonetheless, the lack of clear guideline and commonality elucidation has hindered the clinical translation of RNA drugs. In this review, we outline the mechanisms of action for targeted RNA delivery systems and summarize four key factors that influence the targeting delivery of RNA drugs. These factors include the category of vector materials, chemical structures of vectors, administration routes, and physicochemical properties of RNA vectors, and they all notably contribute to specific organ/tissue tropism. Furthermore, we provide an overview of the main RNA-based drugs that are currently in clinical trials, highlighting their design strategies and tissue tropism applications. This review will aid to understand the principles and mechanisms of targeted delivery systems, accelerating the development of future RNA drugs for different diseases.

Hepatocellular carcinoma (HCC) is one of the most common types of liver cancer; accounts for 75-85% of cases. The treatment and management of HCC involve different sanative options like surgery, chemotherapy, immunotherapy, etc. Recently, various advancements have been introduced for the diagnosis and targeting of hepatic tumor cells. Among these, biomarkers are considered the primary source for the diagnosis and differentiation of tumor cells. With the advancement in the field of nanotechnology, different types of nanocarriers have been witnessed in tumor targeting. Nanocarriers such as nanoparticles, liposomes, polymeric micelles, nanofibers, etc. are readily prepared for effective tumor targeting with minimal side-effects. The emergence of various approaches tends to improve the effectiveness of these nanocarriers as demonstrated in ample clinical trials. This review focuses on the significant role of carbohydrates such as mannose, galactose, fructose, etc. in the development, diagnosis, and therapy of HCC. Hence, the current focus of this review is to acknowledge various perspectives regarding the occurrence, diagnosis, treatment, and management of HCC.

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Although important progress has been made, cancer still remains a complex disease to treat. Serious side effects, the insurgence of resistance and poor selectivity are some of the problems associated with the classical metal-based anti-cancer therapies currently in clinical use. New treatment approaches are still needed to increase cancer patient survival without cancer recurrence. Herein, we reviewed two promising-at least in our opinion-new strategies to increase the efficacy of transition metal-based complexes. First, we considered the possibility of assembling two biologically active fragments containing different metal centres into the same molecule, thus obtaining a heterobimetallic complex. A critical comparison with the monometallic counterparts was done. The reviewed literature has been divided into two groups: the case of platinum; the case of gold. Secondly, the conjugation of metal-based complexes to a targeting moiety was discussed. Particularly, we highlighted some interesting examples of compounds targeting cancer cell organelles according to a third-order targeting approach, and complexes targeting the whole cancer cell, according to a second-order targeting strategy.

Inflammatory bone diseases include osteoarthritis (OA) and rheumatoid arthritis (RA), which can cause severe bone damage in a chronic inflammation state, putting tremendous pressure on the patients\' families and government agencies regarding medical costs. In addition, the complexity of osteoimmunology makes research on these diseases difficult. Hence, it is urgent to determine the potential mechanisms and find effective drugs to target inflammatory bone diseases to reduce the negative effects of these diseases. Recently, pyroptosis, a gasdermin-induced necrotic cell death featuring secretion of pro-inflammatory cytokines and lysis, has become widely known. Based on the effect of pyroptosis on immunity, this process has gradually emerged as a vital component in the etiopathogenesis of inflammatory bone diseases. Herein, we review the characteristics and mechanisms of pyroptosis and then focus on its clinical significance in inflammatory bone diseases. In addition, we summarize the current research progress of drugs targeting pyroptosis to enhance the therapeutic efficacy of inflammatory bone diseases and provide new insights for future directions.

Immunotherapy based on immune checkpoint inhibitors has evolved into a new pillar of cancer treatment in clinics, but dealing with treatment resistance (either primary or acquired) is a major challenge. The tumor microenvironment (TME) has a substantial impact on the pathological behaviors and treatment response of many cancers. The biophysical clues in TME have recently been considered as important characteristics of cancer. Furthermore, there is mounting evidence that biophysical cues in TME play important roles in each step of the cascade of cancer immunotherapy that synergistically contribute to immunotherapy resistance. In this review, we summarize five main biophysical cues in TME that affect resistance to immunotherapy: extracellular matrix (ECM) structure, ECM stiffness, tumor interstitial fluid pressure (IFP), solid stress, and vascular shear stress. First, the biophysical factors involved in anti-tumor immunity and therapeutic antibody delivery processes are reviewed. Then, the causes of these five biophysical cues and how they contribute to immunotherapy resistance are discussed. Finally, the latest treatment strategies that aim to improve immunotherapy efficacy by targeting these biophysical cues are shared. This review highlights the biophysical cues that lead to immunotherapy resistance, also supplements their importance in related technologies for studying TME biophysical cues in vitro and therapeutic strategies targeting biophysical cues to improve the effects of immunotherapy.