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STUDY DESIGN Case series. OBJECTIVES To describe a novel surgical strategy for severe, rigid post-tubercular cervical kyphosis with treatment outcomes in two patients. BACKGROUND DATA Spinal tuberculosis is a common cause of kyphotic deformity in the developing world with 3-5% of non-operatively managed patients ending up with kyphosis exceeding 60°. Ventral, dorsal and combined approaches have been described for cervical kyphosis, but there is no established surgical strategy for severe, rigid post-tubercular cervical kyphosis. METHODS We operated on two girls with severe, rigid cervical kyphosis with preoperative kyphosis measuring 98° and 62°. Our surgical strategy included a three-step approach in the same sitting-(1) An anterior approach to osteotomize the fused vertebral body mass, decompress the spinal cord ventrally and place a temporary cage to stabilize the spine, (2) A posterior approach to osteotomize the fused facets and decompress the cord dorsally. With the completion of the osteotomy, a combination of pedicle screws and lateral mass screws was used to correct the deformity via an anterior opening, posterior closing type of osteotomy. This was followed by, (3) An anterior approach to replace the corpectomy cage with a larger one supplemented with an anterior cervical plate. RESULTS Our 540° approach achieved a substantial improvement in each of the clinical and radiological parameters we measured, viz. C2-C7 lordosis angle, C2-C7 sagittal vertical axis, neck tilt and Neck Disability Index. CONCLUSION For severe, rigid post-tubercular cervical spine kyphosis, a three-step, anterior-posterior-anterior procedure can be used for achieving acceptable correction, improving symptoms and avoiding further progression. LEVEL OF EVIDENCE IV.The regulation of immune checkpoint is a pivotal mechanism mediating both self-tolerance physiologically and tumor immune evasion pathologically. Along with an increasing number of identified checkpoint ligand-receptor pairs, the complexity of regulation at genetic, epigenetic, transcriptional, translational, and post-translational levels makes it highly challenging to assemble a comprehensive regulatory network. Selleckchem GDC-6036 Advanced animal models are required for determining the exact regulatory effects, given the differences in human and mouse immune systems. Our further understanding on checkpoint regulation may energize translational studies aimed to improve cancer immunotherapy, and collaborations between researchers with different expertise would help to tackle existing challenges in this field.Immune checkpoint blockade (ICB) has been proven to be an effective strategy for enhancing the effector activity of anti-tumor T cells, and checkpoint blockers targeting CTLA-4, PD-1, and PD-L1 have displayed strong and durable clinical responses in certain cancer patients. The new hope brought by ICB therapy has led to the boost in therapeutic development of ICBs in recent years. Nonetheless, the therapeutic efficacy of ICBs varies substantially among cancer types and patients, and only a proportion of cancer patients could benefit from ICBs. The emerging targets and molecules for enhancing anticancer immunity may bring additional therapeutic opportunities for cancer patients. The current challenges in the ICB therapy have been discussed, aimed to provide further strategies for maximizing the efficacy of ICB therapy.After decades of intense effort, immune checkpoint inhibitors have been conclusively demonstrated to be effective in cancer treatments and thus are revolutionizing the concepts in the treatment of cancers. Immuno-oncology has arrived and will play a key role in cancer treatment in the foreseeable future. However, efforts to find novel methods to improve the immune response to cancer have not ceased. Small-molecule approaches offer inherent advantages over biologic immunotherapies since they can cross cell membranes, penetrate into tumor tissue and tumor microenvironment more easily, and are amenable to be finely controlled than biological agents, which may help reduce immune-related adverse events seen with biologic therapies and provide more flexibility for the combination use with other therapies and superior clinical benefit. On the one hand, small-molecule therapies can modulate the immune response to cancer by restoring the antitumor immunity, promoting more effective cytotoxic lymphocyte responses, and regulating tumor microenvironment, either directly or epigenetically. On the other hand, the combination of different mechanisms of small molecules with antibodies and other biologics demonstrated admirable synergistic effect in clinical settings for cancer treatment and may expand antibodies' usefulness for broader clinical applications. This chapter provides an overview of small-molecule immunotherapeutic approaches either as monotherapy or in combination for the treatment of cancer.Peptides, as a large group of molecules, are composed of amino acid residues and can be divided into linear or cyclic peptides according to the structure. Over 13,000 molecules of natural peptides have been found and many of them have been well studied. In artificial peptide libraries, the number of peptide diversity could be up to 1 × 1013. Peptides have more complex structures and higher affinity to target proteins comparing with small molecular compounds. Recently, the development of targeting cancer immune checkpoint (CIP) inhibitors is having a very important role in tumor therapy. Peptides targeting ligands or receptors in CIP have been designed based on three-dimensional structures of target proteins or directly selected by random peptide libraries in biological display systems. Most of these targeting peptides work as inhibitors of protein-protein interaction and improve CD8+ cytotoxic T-lymphocyte (CTL) activation in the tumor microenvironment, for example, PKHB1, Ar5Y4 and TPP1. Peptides could be designed to regulate CIP protein degradation in vivo, such as PD-LYSO and PD-PALM. Besides its use in developing therapeutic drugs for targeting CIP, targeting peptides could be used in drug's targeted delivery and diagnosis in tumor immune therapy.