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Cancer Immunotherapies: What the Perioperative Physician Needs to Know.

Purpose of reviewFor patients with cancer, treatment may include combination therapy, including surgery and immunotherapy. Here, we review perioperative considerations for the patient prescribed immunotherapeutic agents.Recent findingsThe perioperative period is a poignant moment in the journey of a patient with cancer, potentially deemed most influential compared to other moments in the care continuum. Several immunotherapeutic medications have been employed near the time of surgery to potentially increase effectiveness. Of the various drug classes, including immune checkpoint inhibitors, cyt

Mesenchymal Stromal Cell Therapy in Solid Organ Transplantation.

Transplantation is the gold-standard treatment for the failure of several solid organs, including the kidneys, liver, heart, lung and small bowel. The use of tailored immunosuppressive agents has improved graft and patient survival remarkably in early post-transplant stages, but long-term outcomes are frequently unsatisfactory due to the development of chronic graft rejection, which ultimately leads to transplant failure. Moreover, prolonged immunosuppression entails severe side effects that severely impact patient survival and quality of life. The achievement of tolerance, i.e., stable graft

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… MSC were shown to also suppress the activation of memory T cells induced by cytokines ( 29 ) or by alloantigens from both minor and major histocompatibility complexes ( 30 , 31 ). …

Innovations in cancer treatment as novel potential and the myth of personalized vaccines, immunotherapy, CRISPR/Cas9, and bacteriotherapy as promising therapeutic strategies.

Recent advancements in cancer treatment, including targeted therapy, tailored vaccines, immunotherapy, and bacteriotherapy, have demonstrated remarkable potential in addressing various types of cancer. However, the pursuit of novel therapeutic strategies remains challenged by significant obstacles, including toxicity to healthy tissues, limited penetration into malignant tissues, and the potential for tumor cell resistance to pharmacological agents. This study explored the potential of tailored vaccinations, immunotherapy, CRISPR/Cas9, and bacteriotherapy for cancer treatment. Randomized and n

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… Following that, it proceeds through processing and presentation via the major histocompatibility complex (MHC) class I route. Bacterial species are involved in the synthesis of LLO, a protein that is mostly located inside the cytoplasmic compartment. …

Nanomedicine for cancer patient-centered care.

Cancer is a leading cause of morbidity and mortality worldwide, and an increase in incidence is estimated in the next future, due to population aging, which requires the development of highly tolerable and low-toxicity cancer treatment strategies. The use of nanotechnology to tailor treatments according to the genetic and immunophenotypic characteristics of a patient's tumor, and to allow its targeted release, can meet this need, improving the efficacy of treatment and minimizing side effects. Nanomedicine-based approach for the diagnosis and treatment of cancer is a rapidly evolving field. Se

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… Immunostimulatory agents include cytokines, such as IL‐2, which has been approved by the US FDA for treating metastatic melanoma and renal cell carcinoma 98 , 99 or IFNs, such as IFNα, which promotes major histocompatibility complex class I expression leading to better tumor antigen recognition, and …

The use of RNA-based treatments in the field of cancer immunotherapy.

Over the past several decades, mRNA vaccines have evolved from a theoretical concept to a clinical reality. These vaccines offer several advantages over traditional vaccine techniques, including their high potency, rapid development, low-cost manufacturing, and safe administration. However, until recently, concerns over the instability and inefficient distribution of mRNA in vivo have limited their utility. Fortunately, recent technological advancements have mostly resolved these concerns, resulting in the development of numerous mRNA vaccination platforms for infectious diseases and various t

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… Adaptive immunity is initiated when APCs take in and proteolytically digest antigens, then present them on major histocompatibility complexes (MHCs) of the class I and class II kind to helper T cells (CD8 + and CD4 + T cells) [ 167 ]. …

Targeting B Cell Maturation Antigen in Patients with Multiple Myeloma: Current Perspectives.

Relapsed/refractory multiple myeloma remains a challenging disease necessitating the development of more effective treatment options. In the past decade, myeloma therapies have made significant advancements with the introduction of new treatment modalities. One of the new major targets for these novel therapeutics has been B-cell maturation antigen (BCMA), which is expressed on mature B-lymphocytes and plasma cells. There are three main categories of BCMA-targeted therapies currently available, including bispecific antibodies (BsAbs), antibody drug conjugates (ADCs), and chimeric antigen recep

Epigenetic and Transcriptomic Regulation Landscape in HPV+ Cancers: Biological and Clinical Implications.

Human Papillomavirus (HPV) is an oncogenic virus that causes the highest number of viral-associated cancer cases and deaths worldwide, with more than 690,000 new cases per year and 342,000 deaths only for cervical cancer (CC). Although the incidence and mortality rates for CC are declining in countries where screening and vaccination programs have been implemented, other types of cancer in which HPV is involved, such as oropharyngeal cancer, are increasing, particularly in men. Mutational and transcriptional profiles of various HPV-associated neoplasms have been described, and accumulated evid

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… Studies have shown that E5 plays an essential role in carcinogenesis, as it is critical in cell transformation and immune modulation by interacting with the major histocompatibility complex class I (MHC-class I). …

Клетки T-бет+CXCR3+B вызывают гиперреактивное взаимодействие клеток B-T в множестве склерозов.

Множественный склероз (MS) — аутоиммунное заболевание центральной нервной системы (CNS). Одним из ключевых механизмов в НР является автораспространение (АП) ячеек В и Т, основанное на самопропитании. Здесь мы показываем, что про-воспаление B-T-обогащенные клетки клеток (BTEC) формируются во время AP и зеркальные особенности реакции микроцентра. T-bet+CXCR3+B — основной подмножество клеток, усиливающих и поддерживающих свои параллельные клетки TH1 с помощью интерферона (IFN)-__, и присутствуют в сильно воспламенённой менингетной ткани. Фундаментальная сигнатура активации клеток В находит свое о

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… Administration of IFN-γ in a clinical trial worsened MS. 77 IFN-γ has been shown to lead to synapse loss 78 and to cause hypomyelination, reactive gliosis, 79 and upregulation of major histocompatibility complex class II on several brain cell types including neurons and oligodendrocytes, 80 , 81 …

Pulmonary and Hepatic Complications of Hematopoietic Cell Transplantation

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… In addition to being directly cytotoxic, TNFα increases expression of inflammatory chemokines (Hildebrandt et al. 2004 ) and major histocompatibility complex (MHC) antigens, modulates leukocyte migration, and facilitates cell-mediated cytotoxicity, including endothelial cell injury, a common feature …

Advancing CRISPR genome editing into gene therapy clinical trials: progress and future prospects.

Genome editing has recently evolved from a theoretical concept to a powerful and versatile set of tools. The discovery and implementation of CRISPR-Cas9 technology have propelled the field further into a new era. This RNA-guided system allows for specific modification of target genes, offering high accuracy and efficiency. Encouraging results are being announced in clinical trials employed in conditions like sickle cell disease (SCD) and transfusion-dependent beta-thalassaemia (TDT). The path finally led the way to the recent FDA approval of the first gene therapy drug utilising the CRISPR/Cas

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… Firstly, aiming to block the host-versus-graft disease (HVGD), class 1 major histocompatibility complex (MHC I) is eliminated by knocking out the β2 M subunit (Ref 71 ). This increases persistence and the chance for durable remissions. …

Exogenous Heat Shock Proteins in Oncology: Biological Roles and Clinical Implications.

Heat shock proteins (HSPs), particularly HSP70 and HSP90, are highly conserved molecular chaperones that protect cells from a wide range of stressors and maintain proteome homeostasis. In cancer, tumor cells frequently overexpress and actively release HSPs into the extracellular space and circulation in response to metabolic alterations, hypoxia, oxidative stress, and therapeutic interventions. Consequently, circulating HSP levels are often elevated in patients with malignancies compared with healthy individuals. This review summarizes current evidence on the diagnostic, prognostic, and predic

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… After internalization, HSP90 transports the antigen through the Sec61 translocon into the cytosol [ 107 , 109 ]; the proteasome then generates peptides loaded onto major histocompatibility complex class I, activating CD8+ cytotoxic T-lymphocytes [ 107 , 109 ]. …

Множественные модели миэломы и витро человека для моделирования заболеваний и скрининга на лечение.

Множественная миелома (ММ) — гематологическая порча, характеризующаяся неконтролируемым расширением злокачественных плазменных клеток в микроокружающей среде костного мозга. В то время как культуры подвески клеточных линий MM и мусриновых моделей были краеугольным камнем исследований MM патогенез, эти традиционные системы не могут воспроизвести критические аспекты микроопухоли человека. В частности, нынешние модели неадекватно учитывают ключевые биологические вопросы, включая механизмы приобретения лекарственного сопротивления, стратегии уклонения от иммунитета и роль клеточного перекрестка в

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… The importance of using gene-edited iPSCs is exemplified by CRISPR-Cas9-mediated disruption of Beta 2-microglobulin (B2M) and major histocompatibility complex II (CIITA) genes in the MUSIi001-A-2 line, which eliminates human leukocyte antigen (HLA) class I and II expression and generates “universal” …

Harnessing live vectors for cancer vaccines: Advancing therapeutic immunotherapy.

Cancer vaccines represent a promising approach within immunotherapies. These vaccines are tailored to target tumor-specific antigens, thereby offering a precision approach to cancer treatment. The key principles in developing therapeutic cancer vaccines include identifying appropriate vaccine targets and selecting effective vaccine delivery platforms. These delivery platforms are diverse and have evolved to enhance the immune response. This review explores live cancer vaccines and the biological entities involved. Live cancer vaccines leverage the use of various biological entities to stimulat

KDIGO Clinical Practice Guideline on the Evaluation and Care of Living Kidney Donors.

The 2017 Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline on the Evaluation and Care of Living Kidney Donors is intended to assist medical professionals who evaluate living kidney donor candidates and provide care before, during and after donation. The guideline development process followed the Grades of Recommendation Assessment, Development, and Evaluation (GRADE) approach and guideline recommendations are based on systematic reviews of relevant studies that included critical appraisal of the quality of the evidence and the strength of recommendations. However, m

Использование микробиомных средств для совершенствования методов лечения нейродегенеративных заболеваний: данные о воздействии вдоль оси микробиота-гут-мозгов.

Недавно в качестве полезной модели для понимания возникновения и развития нейродегенеративных заболеваний (НДД) появилась ось микробиота-гут-мозгов (МГБА). Меры воздействия на основе микробиома с использованием биотических добавок (пробиотики, предбиотики, синдиотики, постбиотики) могут модифицировать MGBA и служить подходящими решениями для снижения риска неврологических изменений, связанных с НИЗ, и регулирования симптомов. В настоящем описательном обзоре содержится резюме функционирования МГБС и его взаимодействия с заболеваниями, связанными с началом и развитием НИЗ. Проводится обзор мероп

Cancer Immunotherapy with Immune Checkpoint Inhibitors-Biomarkers of Response and Toxicity; Current Limitations and Future Promise.

Immune checkpoint inhibitors are monoclonal antibodies that are used to treat over one in three cancer patients. While they have changed the natural history of disease, prolonging life and preserving quality of life, they are highly active in less than 40% of patients, even in the most responsive malignancies such as melanoma, and cause significant autoimmune side effects. Licenced biomarkers include tumour Programmed Death Ligand 1 expression by immunohistochemistry, microsatellite instability, and tumour mutational burden, none of which are particularly sensitive or specific. Emerging tumour

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… The more mutations the more neo-antigens are potentially coded for and presented to the immune system by the tumour cell via Major Histocompatibility Complex I (MHC I, also known as Human Leukocyte Antigen I (HLA I)). …

Integrating oncolytic adenoviruses into combination cancer therapy: Mechanisms, advances and clinical outlook.

BACKGROUND: Cancer represents a major global public health issue, and recent research has focused on improving the efficacy of existing therapeutic approaches. In this context, oncolytic viruses have emerged as promising treatment options for advanced and treatment-resistant malignancies. Among them, adenoviruses are the most extensively studied due to their favourable safety profile, biological versatility and ease of genetic modification to enhance therapeutic performance. MAIN BODY: Combination-based strategies integrating virotherapy with chemotherapy, radiotherapy or immunotherapy have b

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… McSharry BP, Burgert H‐G, Owen DP, et al. adenovirus E3/19K promotes evasion of NK cell recognition by intracellular sequestration of the NKG2D ligands major histocompatibility complex class I chain‐related proteins A and B. J Virol. 2008;82(9):4585‐4594. 58. Zhang J, Zhang Q, Liu Z, et al. …

Unraveling the triad of immunotherapy, tumor microenvironment, and skeletal muscle biomechanics in oncology.

The intricate interaction between skeletal muscle biomechanics, the tumor microenvironment, and immunotherapy constitutes a pivotal research focus oncology. This work provides a comprehensive review of methodologies for evaluating skeletal muscle biomechanics, including handheld dynamometry, advanced imaging techniques, electrical impedance myography, elastography, and single-fiber experiments to assess muscle quality and performance. Furthermore, it elucidates the mechanisms, applications, and limitations of various immunotherapy modalities, including immune checkpoint inhibitors, adoptive ce

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… CD8+ T cells recognize major histocompatibility complex (MHC) class I molecules on the surface of tumor cells via T cell receptors (TCRs) to induce tumor cell cytotoxicity. …

Immune checkpoint and inflammation as therapeutic targets in pancreatic carcinoma.

Pancreatic adenocarcinoma (PAC) is one of the most deadly malignant neoplasms, and the efficacy of conventional cytotoxic chemotherapy is far from satisfactory. Recent research studies have revealed that immunosuppression and inflammation are associated with oncogenesis, as well as tumor development, invasion, and metastasis in PAC. Thus, immunosuppression-related signaling, especially that involving immune checkpoint and inflammation, has emerged as novel treatment targets for PAC. However, PAC is an immune-resistant tumor, and it is still unclear whether immune checkpoint or anti-inflammatio

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… T cells recognize tumor-associated antigens (TAAs) presented by the major histocompatibility complex class II from APCs or tumor cells through the T-cell receptor. Simultaneously, costimulatory signals are needed to determine whether T cells activate or inhibit immune responses. …

The role of interleukin 17 in tumour proliferation, angiogenesis, and metastasis.

With 7.6 million deaths globally, cancer according to the World Health Organisation is still one of the leading causes of death worldwide. Interleukin 17 (IL-17) is a cytokine produced by Th17 cells, a T helper cell subset developed from an activated CD4+ T-cell. Whilst the importance of IL-17 in human autoimmune disease, inflammation, and pathogen defence reactions has already been established, its potential role in cancer progression still needs to be updated. Interestingly studies have demonstrated that IL-17 plays an intricate role in the pathophysiology of cancer, from tumorigenesis, prol

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… The activation of this has been associated with subsequent tumour shrinkage via IL-2 and major histocompatibility complex/peptide (pMHC)-I [ 47 ]. This enables the activation of the local immunity through the stimulation of an antitumour T-cell response [ 48 ]. …