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Colorectal Cancer at the Crossroads: The Good, the Bad, and the Future of Platinum-Based Drugs.

Colorectal cancer (CRC) remains a significant global health challenge, ranking third in incidence and second in mortality among cancers worldwide. This review addresses the complex landscape of CRC, focusing on incidence, mortality trends, preventive strategies, and the evolving therapeutic approaches, particularly highlighting the role of platinum-based drugs like oxaliplatin (OXP). It also underscores the increasing burden of CRC, with factors such as westernized diets, aging populations, and genetic predispositions contributing to its prevalence. Therapeutically, early detection greatly enh

Lung cancer immunotherapy: progress, pitfalls, and promises.

Lung cancer is the primary cause of mortality in the United States and around the globe. Therapeutic options for lung cancer treatment include surgery, radiation therapy, chemotherapy, and targeted drug therapy. Medical management is often associated with the development of treatment resistance leading to relapse. Immunotherapy is profoundly altering the approach to cancer treatment owing to its tolerable safety profile, sustained therapeutic response due to immunological memory generation, and effectiveness across a broad patient population. Different tumor-specific vaccination strategies are

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… Lung cancer immunotherapy is challenging as the cells avoid immunosurveillance and reduce the overall immunological response by modulating the T-cell mediated cytotoxicity, secretion of immune-suppressive cytokines, and loss of major histocompatibility complex (MHC) expression [ 27 ]. …

Contribution of Macrophages and T Cells in Skeletal Metastasis.

Bone is a common site for metastases with a local microenvironment that is highly conducive for tumor establishment and growth. The bone marrow is replete with myeloid and lymphoid linage cells that provide a fertile niche for metastatic cancer cells promoting their survival and growth. Here, we discuss the role of macrophages and T cells in pro- and anti-tumoral mechanisms, their interaction to support cancer cell growth, and their contribution to the development of skeletal metastases. Importantly, immunotherapeutic strategies targeting macrophages and T cells in cancer are also discussed in

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… The TCRs only recognize antigens when they are loaded onto and presented to the TCRs by the major histocompatibility complex (MHC) molecules. …

Therapeutic Vaccination in Head and Neck Squamous Cell Carcinoma-A Review.

Therapeutic vaccination is one of the most effective immunotherapeutic approaches, second only to immune checkpoint inhibitors (ICIs), which have already been approved for clinical use. Head and neck squamous cell carcinomas (HNSCCs) are heterogenous epithelial tumors of the upper aerodigestive tract, and a significant proportion of these tumors tend to exhibit unfavorable therapeutic responses to the existing treatment options. Comprehending the immunopathology of these tumors and choosing an appropriate immunotherapeutic maneuver seems to be a promising avenue for solving this problem. The c

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… A group of investigators from France has identified four novel major histocompatibility complex (MHC) class II–restricted peptides derived from hTERT as “ Universal Cancer Peptides ” (UCP), and have validated their ability to induce a tumor-specific immune response [ 143 , 144 ]. …

mRNA vaccine development and applications: A special focus on tumors (Review).

Cancer is characterized by unlimited proliferation and metastasis, and traditional therapeutic strategies usually result in the acquisition of drug resistance, thus highlighting the need for more personalized treatment. mRNA vaccines transfer the gene sequences of exogenous target antigens into human cells through transcription and translation to stimulate the body to produce specific immune responses against the encoded proteins, so as to enable the body to obtain immune protection against said antigens; this approach may be adopted for personalized cancer therapy. Since the recent coronaviru

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… The endoplasmic reticulum is where antigenic peptide epitopes are transferred, loaded onto class I molecules of the major histocompatibility complex (MHC I) and presented to CD8 + cytotoxic T-cells. …

Application of single-cell and spatial omics in deciphering cellular hallmarks of cancer drug response and resistance.

Drug resistance poses a significant challenge in cancer therapy, contributing to rapid recurrence, disease progression, and high patient mortality. Despite its critical impact, few reliable predictors for cancer drug response or failure have been established for clinical application. Tumor heterogeneity and the tumor microenvironment (TME) are pivotal factors influencing cancer drug efficacy and resistance. Tumor heterogeneity leads to variable therapeutic responses among patients, while dynamic interactions between cancer cells and the TME enhance tumor survival and proliferation, underscorin

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… The TCR recognizes antigenic peptides that bind to the major histocompatibility complex (MHC), thereby activating T cells to perform their immune functions, while the BCR directly recognizes free antigens and activates B cells to produce specific antibodies that neutralize or eliminate the antigen [ …

T-Regulatory Cells In Tumor Progression And Therapy.

Regulatory T cells (Tregs) are important members of the immune system regulating the host responses to infection and neoplasms. Tregs prevent autoimmune disorders by protecting the host-cells from an immune response, related to the peripheral tolerance. However, tumor cells use Tregs as a shield to protect themselves against anti-tumor immune response. Thus, Tregs are a hurdle in achieving the complete potential of anti-cancer therapies including immunotherapy. This has prompted the development of novel adjuvant therapies that obviate their negative effects thereby enhancing the therapeutic ef

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… Irradiation of tumors releases tumor-specific antigens leading to the immune recognition of tumor-related new peptides by increasing major histocompatibility complex-I molecules (MHC-I), besides up-regulating the expression of Fas antigen, to activate the T-cell mediated cytotoxicity. 12 , 142 , 143 …

Natural killer cells, macrophages and dendritic cells as innate immune therapies for blood cancers.

Innate immune cells are emerging as powerful allies in the fight against blood cancers. Natural Killer (NK) cells, macrophages, and dendritic cells (DCs)—once viewed mainly as supporting players—are now at the forefront of next-generation immunotherapies, owing to their rapid, antigen-independent tumor recognition and potent effector functions. This review highlights their distinct anti-tumor roles: NK cells’ cytotoxicity and “missing-self” recognition, the dual and adaptable nature of macrophages in the tumor microenvironment (TME), and the antigen-presenting capabilities of DCs that bridge i

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… Through this process, NK cells efficiently detect and rapidly destroy tumor cells that have downregulated their Major Histocompatibility Complex class I (MHC-I) expression [ 1 , 15 ]. …

Mucosal-Associated Invariant T Cells Display Diminished Effector Capacity in Oesophageal Adenocarcinoma.

Oesophageal adenocarcinoma (OAC) is an aggressive malignancy with poor prognosis, and incidence is increasing rapidly in the Western world. Mucosal-associated invariant T (MAIT) cells recognize bacterial metabolites and kill infected cells, yet their role in OAC is unknown. We aimed to elucidate the role of MAIT cells during cancer development by characterizing the frequency, phenotype, and function of MAIT cells in human blood and tissues, from OAC and its pre-malignant inflammatory condition Barrett's oesophagus (BO). Blood and tissues were phenotyped by flow cytometry and conditioned media

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… An invariant T cell receptor alpha chain defines a novel TAP-independent major histocompatibility complex class Ib-restricted alpha/beta T cell subpopulation in mammals . J Exp Med. ( 1999 ) 189 : 1907 – 21 . 10.1084/jem.189.12.1907 10377186 PMC2192962 5. …

Nanoparticle-based strategy in CAR-T cell immunotherapy: challenges, implications, and perspectives.

Chimeric antigen receptor (CAR)-T cell therapy has achieved remarkable progress in treating hematologic malignancies, yet its broader application faces challenges such as manufacturing complexity, solid tumor microenvironment barriers, and immune toxicity. Nanoparticles (NPs), leveraging their precise delivery, immunomodulation, and multifunctional integration capabilities, offer innovative strategies to optimize CAR-T cell therapy. This review provides a comprehensive elucidation of the fundamental framework of CAR-T cell therapy and the challenges in oncological applications. Subsequently, w

Антивоспламенительный макропхаж-сухие экзосомы, модифицированные с помощью самоантигенных пептидов для лечения экспериментального аутоиммунного энцефаломелита.

Текущее лечение аутоиммунных заболеваний часто сопряжено с широкодействующими иммунодепрессантами, которые сопряжены с такими рисками, как инфекционные заболевания и болезни. В ходе этого исследования изучается вопрос о том, могут ли экзосомы, полученные из антивоспалительных макрофаг (АЭ) и украшенные миэлином олигодендроцитом гликопротеином (МОГ) пептидом (АЭ/М), способствовать иммунной терпимости при аутоиммунных заболеваниях. Экспериментальный аутоиммунный энцефаломиэлит (EAE), модель мыши для множественных склерозов, служит моделью аутоиммунных заболеваний. Экзосомы, получаемые из миоблас

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… Flow cytometry analysis revealed that proinflammatory markers, including TNF‐ α , major histocompatibility complex class II molecule (MHCII), CD80, CD86, and interleukin 6 (IL‐6), had significantly lower expression levels in the AE/M‐treated group compared to other groups ( Figures 3 A–D and S6A …

Широкие повреждения обода являются новым патологическим и визуализированным биомаркером для быстрого развития заболеваний в множестве склерозов.

Текущее несколько методов лечения склероза (MS) сокращают активность рецидивов, но оказывают ограниченное воздействие на прогрессию заболеваний. Клинические испытания, ориентированные на прогресс, часто не дают результатов из-за недостаточного понимания его основополагающих механизмов. В этом исследовании анализировалась клинически хорошо известная когорта вскрытия MS из банка мозга Негерланда (186 человек), из которого мы отобрали доноров, проявляющих противоположные траектории заболеваний медленных и быстрых темпов развития. Мы провели обширную непредвзятую гистологию и пространственную тран

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… MHC, major histocompatibility complex. Source data Spatial transcriptomic analysis of CD68 pos myeloid cells in BRL lesion rims, mixed lesion rims and active lesion centers as compared to normal appearing white matter (NAWM). …

Evans syndrome: clinical perspectives, biological insights and treatment modalities.

Evans syndrome (ES) is a rare and chronic autoimmune disease characterized by autoimmune hemolytic anemia and immune thrombocytopenic purpura with a positive direct anti-human globulin test. It is classified as primary and secondary, with the frequency in patients with autoimmune hemolytic anemia being 37%-73%. It predominates in children, mainly due to primary immunodeficiencies or autoimmune lymphoproliferative syndrome. ES during pregnancy is associated with high fetal morbidity, including severe hemolysis and intracranial bleeding with neurological sequelae and death. The clinical presenta

Nanomedicine and Onco-Immunotherapy: From the Bench to Bedside to Biomarkers.

The broad relationship between the immune system and cancer is opening a new hallmark to explore for nanomedicine. Here, all the common and synergy points between both areas are reviewed and described, and the recent approaches which show the progress from the bench to the beside to biomarkers developed in nanomedicine and onco-immunotherapy.

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… In the case of aAPCs, dextran-conjugated superparamagnetic iron oxide NPs with major histocompatibility complex (MHC)-Ig dimer and anti-CD28 antibody are used. Magnetic field-induced aAPCs stimulate the activation and proliferation of antigen-specific T-lymphocytes [ 46 ]. ii. …

Emerging Immunotherapy and Antibody-Derived Therapeutics for the Treatment of Advanced Non-Small-Cell Lung Cancer: A Review.

Background: In the last decade, a surge of advancements in and approvals of immunotherapies has revolutionized the treatment of non-small-cell lung cancer (NSCLC). Even as an increasing number of immune checkpoint inhibitors and antibody-drug conjugates gained FDA approval for the remarkable response and durable remission they imparted to some patients, persistent challenges of primary and acquired resistance, imperfect predictive biomarkers, and toxicity remain. Methods: This review identifies and summarizes the most significant emerging clinical data being reported for immunotherapies in NSC

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… In contrast to TILs, CAR T-cell therapies, and TCR-T therapy, NK cells detect loss of major histocompatibility complex (MHC) expression, which is a common mode of tumor immune evasion. …

The JAK/STAT signaling pathway: from bench to clinic.

The Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway was discovered more than a quarter-century ago. As a fulcrum of many vital cellular processes, the JAK/STAT pathway constitutes a rapid membrane-to-nucleus signaling module and induces the expression of various critical mediators of cancer and inflammation. Growing evidence suggests that dysregulation of the JAK/STAT pathway is associated with various cancers and autoimmune diseases. In this review, we discuss the current knowledge about the composition, activation, and regulation of the JAK/STAT pat

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… STAT1 participates in all major histocompatibility complex (MHC)-dependent antigen presentation processes. 86 In addition, STAT1 is involved in the early development of B cells. 87 , 88 The absence of STAT1 or a mutation in the STAT1 gene increases the body’s susceptibility to parasites, bacteria, viruses … histocompatibility complex STAT | Cytokine and growth factor | Biological functions STAT1 | All interferons, IL-2, IL-6, PDGF, EGF, HGF, TNF, angiotensin II | (1) Regulate cell growth and differentiation; (2) Promote cell apoptosis; (3) Inhibit tumor occurrence; (4) Regulate immune response. …

Beneath the surface in autoimmune hemolytic anemia: pathogenetic networks, therapeutic advancements and open questions.

In recent years, the pathophysiologic framework of autoimmune hemolytic anemias (AIHAs) has evolved considerably, extending beyond the simplistic paradigm of antibody-mediated red blood cell (RBC) destruction, which is now recognized as a downstream consequence of a broader immune dysregulation. AIHA is fundamentally orchestrated by a complex interplay between innate and adaptive immune components, including autoreactive B and T lymphocytes, macrophages, and the reticuloendothelial system. Central to disease pathogenesis are two interrelated mechanisms: clonal B-cell expansion with autoantibod

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… Thymocytes expressing T cell receptors (TCRs) that fail to engage self-peptides presented via major histocompatibility complex (MHC) molecules undergo death by neglect due to insufficient survival signaling ( 67 ). …

Вирусная инфекция Эпштейна-Барра поощряет диагностику Т клеток в гуманизированной модели мыши множественного склероза.

Скрытая инфекция вируса Эпштейн-Барр (ЭБВ) является серьезным фактором риска для развития множественных склерозов (МС), хотя основополагающие механизмы остаются неясными. Для изучения этой связи мы спровоцировали экспериментальный аутоиммунный энцефаломиелит (EAE) в мышах с иммунодефицитными мышами, восстановленных с периферийными моноядерными клетками крови (PBMC) у лиц, которые имели или не имели историю заражения EBV и/или повторного образования MS (RMS). Мыши HuPBMC EAE, генерируемые EBV-серонегативными здоровыми донорами, были менее восприимчивы к возникновению серьезных неврологических с

Advancing gene editing therapeutics: Clinical trials and innovative delivery systems across diverse diseases.

Gene editing is a groundbreaking therapeutic approach that can potentially treat a broad spectrum of genetic and acquired diseases. This review highlights recent clinical trials employing advanced gene editing technologies such as CRISPR-Cas9, zinc-finger nucleases (ZFNs), and base editors across multiple disease areas including metabolic disorders, autoimmune diseases, muscular dystrophies, and inherited eye disorders. Central to the success of these therapies is the development of efficient and safe delivery systems, including lipid nanoparticles (LNPs), viral vectors (adenoviral and lentivi

Emerging Frontiers in Colorectal Cancer Therapy: From Targeted Molecules to Immunomodulatory Breakthroughs and Cell-Based Approaches.

Colorectal cancer (CRC) is ranked as the second leading cause of cancer-related deaths globally, necessitating urgent advancements in therapeutic approaches. The emergence of groundbreaking therapies, including chimeric antigen receptor-T (CAR-T) cell therapies, oncolytic viruses, and immune checkpoint inhibitors, marks a transformative era in oncology. These innovative modalities, tailored to individual genetic and molecular profiles, hold the promise of significantly enhancing patient outcomes. This comprehensive review explores the latest clinical trials and advancements, encompassing targe

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… They can activate antigen-presenting cells, which help to present epitopes on the major histocompatibility complex class I (MHC-I), thereby promoting the activity of cytotoxic T lymphocytes. This process can lead to the destruction of cancer cells [ 22 ]. …