Immunocheckpoints

BACKGROUND: In recent years, the emergence of immunotherapy has renewed therapeutic modality. Different from traditional anti-tumor therapy, immune-related adverse events of skin, gastrointestinal tract, liver, lung, endocrine glands commonly occurred. At present, only one case of immune-related adverse event of Behcet's-like syndrome following pembrolizumab treatment was reported in USA, and no one is reported in China. CASE PRESENTATION: Here, we report a rare case of Behcet's-like symptom following pembrolizumab treatment...

Aim: This study aims to clarify the efficacy and adverse effects of immune checkpoint inhibitors (ICIs) in the lung cancer patients with a history of interstitial lung disease (ILD). Methods: From the inception of the database to 4 April 2023, we systematically searched the four databases. Results: The objective remission rate, disease control rate, incidence of immune-associated pneumonitis (ICIP) in the combined ILD group were significantly higher than those in the non-combined ILD group. There were no significant differences between the two groups in progression-free survival, overall survival, renal insufficiency, thyroid dysfunction and gastrointestinal toxicity...

RNA m6 methyladenosine (m6A) modifications impact tumor biology and immune processes, particularly in hepatocellular malignant tumors. Using a consensus clustering algorithm on 371 hepatocellular carcinoma (HCC) samples, we identified three m6A-modified subtypes and correlated them with positive tumor microenvironment (TME) markers for distinct immune phenotypes. Stratifying patients based on m6A scores revealed a low presentation group with better immune penetration, lower tumor mutation load, and increased expression of immune checkpoint markers like CTLA-4 and PD-1, suggesting enhanced responsiveness to immunization therapy...

Tumor immunotherapy, which targets immune checkpoints, presents a promising strategy for the treatment of various cancer types. However, current clinical data indicate challenges in its application to solid tumors. Recent studies have revealed a significant correlation between the degree of immune response in immunotherapy and the tumor microenvironment, particularly with regard to tumor-infiltrating immune cells. Among these immune cells, macrophages, a critical component, are playing an increasingly vital role in tumor immunotherapy...

With changes in modern lifestyles, type 2 diabetes mellitus (T2DM) has become a global epidemic metabolic disease, and hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide. T2DM is a complex metabolic disorder and has been considered an independent risk factor for HCC. Growing evidence supports that T2DM-related risk factors facilitate hepatocarcinogenesis via abundant mechanisms. With the wide implementation of microbiomics, transcriptomics, and immunotherapy, the understanding of the complex mechanisms of intestinal flora and immune cell subsets have advanced tremendously in T2DM-related HCC, uncovering new findings in T2DM-related HCC patients...

Immunotherapy has been proven a viable treatment option for non-small cell lung cancer (NSCLC) treatment in patients. However, some patients still do not benefit. Finding new predictive biomarkers for immunocheckpoint inhibitor (ICI) response will improve treatment management in the clinical routine. In this regard, liquid biopsy is a useful and noninvasive alternative to surgical biopsies. In the present study, we evaluated the potential diagnostic, prognostic, and predictive value of seven different soluble mediators involved in immunoregulation...

Immunocheckpoint inhibitors have shown impressive efficacy in patients with colon cancer as well as other types of solid tumor that are mismatch repair-deficient (dMMR). Currently, polymerase chain reaction (PCR)-capillary electrophoresis (CE) is one of the mainstream detection methods for dMMR, but its accuracy is still limited by germline MMR mutations, the functional redundancy of the MMR system and abnormal methylation of MLH1 promoter. Therefore, this study aims to develop new biomarkers for dMMR based on Artificial Intelligence (AI) and pathological images, which may help to improve the detection accuracy...

Endocrinopathies, especially hypothyroidism, are very frequent during immunocheckpoint inhibitors treatment. An early diagnosis, through a correct clinical evaluation and the execution of blood tests, and the use of Levothyroxine therapy, allow you to continue the established tretament in most cases.

Colorectal cancer (CRC) is the third most frequent cancer and the second leading cause of cancer-related deaths in Europe. About 5% of metastatic CRC (mCRC) are characterized by high microsatellite instability (MSI) due to a deficient DNA mismatch repair (dMMR), and this condition has been related to a high sensitivity to immunotherapy, in particular to the Immune Checkpoint Inhibitors (ICIs). In fact, in MSI-H or dMMR mCRC, treatment with ICIs induced remarkable response rates and prolonged survival. However, the majority of mCRC cases are mismatch-repair-proficient (pMMR) and microsatellite-stable (MSS), and unfortunately these conditions involve resistance to ICIs...

The alteration of the gut microbiota mediated by proton pump inhibitor (PPI) drugs could be involved in the clinical response associated with immunotherapy [immunocheckpoint inhibitors (ICIs)] in cancer patients. Due to the current controversy in the scientific evidence, it has been proposed to evaluate the correlation between the concomitant use of PPIs and the effectiveness of immunotherapy in a real clinical practice setting. Single-center retrospective cohort study that included patients treated with anti-PD-1 or anti-CTLA4, including nivolumab, pembrolizumab, atezolizumab, or the combination ipilimumab-nivolumab in metastatic neoplastic disease...

The treatment of locally advanced (LA) Head and Neck Squamous Cell Carcinoma (HNSCC) is based on surgery followed by (chemo)radiation or on curative (chemo)radiation, depending on site and stage. Despite optimal locoregional treatment, about 50% of patients recur, with a huge impact on prognosis and substantial morbidity. The advent of immunotherapy (IT) with immune checkpoint inhibitors (ICIs) changed the paradigm of systemic treatment for recurrent/metastatic (RM) disease, showing activity, efficacy, and safety in both platinum-resistant and platinum-naïve patients...

Local radio-therapy combined with immunotherapy has attracted great interest in controlling local tumors. In this study, we have developed membrane-cloaked manganese dioxide nanoparticles displaying anti-PD-L1 antibodies as targeted immuno-radio-enhancers. Mediated by anti-PD-L1 antibodies (aPD-L1) expressed on cell membranes, this kind of membrane-coated nanosystem can selectively deliver cytosine-phosphate-guanine (CpG)-loaded MnO2 nanoparticles (NPs) and induce systemic anti-tumor immunities, thereby achieving favorable immuno/radio-therapeutic outcomes...

Epithelioid trophoblastic tumor (ETT) is a rare gestational trophoblastic tumor, first described by Shih and Kurman in 1998. ETT often present as abnormal vaginal bleeding in women of reproductive age, but unlike more common forms of GTN tend to produce much less human chorionic gonadotropin (hCG) for the volume of disease present. ETT can occur after any gestational event and can occur in both intrauterine and extrauterine sites. We present a case of a 46-year-old female patient incidentally diagnosed with ETT and hepatic metastasis...

BACKGROUND: Positron emission tomography (PET) with the use of 18F-fluorodeoxyglucose (FDG), implemented with low dosage Computer Tomography (CT), is to be considered as the most important evolution of imaging in the management and assessment of classical Hodgkin Lymphoma (cHL) patients. SUMMARY: According to Lugano response criteria, FDG-PET is mandatory to define metabolic response to frontline therapy and moreover it is important in the definition of non-responders or refractory disease patients...

BACKGROUND: SETD2 protects against genomic instability via maintenance of homologous recombination repair (HRR) and mismatch repair (MMR) in neoplastic cells. However, it remains unclear whether SETD2 dysfunction is a complementary or independent factor to microsatellite instability-high (MSI-H) and tumor mutational burden-high (TMB-H) for immunocheckpoint inhibitor (ICI) treatment, and little is known regarding whether this type of dysfunction acts differently in various types of cancer...

BACKGROUND: Immunocheckpoint inhibitor(ICI) is a major breakthrough in tumor treatment. It can activate the patient's own immune system and play an anti-tumor role, but not all patients can benefit from it. At present, there is still a lack of effective biomarkers to guide clinical application. The systemic immune inflammation(SII) index reflects the systemic inflammatory state and immune state of patients. Prognostic nutrition index(PNI) can be used to evaluate immune status of patients...

BACKGROUNDS: PD-1 inhibitors and TKIs have been used to treat advanced osteosarcoma, but there is still a lack of intuitive data for the comparison of their efficacy. We conducted a meta-analysis to evaluate their therapeutic benefits. METHODS: A systematic methodological search of five primary electronic databases was performed. Studies with a randomized design of any type about PD-1 inhibitors or TKIs for the treatment of advanced osteosarcoma were included. The primary outcomes mainly included CBR, PFS, OS and ORR, The CR, PR, SD and AEs were the secondary outcomes...

The poor survival of triple-negative breast cancer (TNBC) is due to its aggressive behavior, large heterogeneity, and high risk of recurrence. A comprehensive molecular investigation of this type of breast cancer using high-throughput next-generation sequencing (NGS) methods may help to elucidate its potential progression and discover biomarkers related to patient survival. In this review, the NGS applications in TNBC research are described. Many NGS studies point to TP53 mutations, immunocheckpoint response genes, and aberrations in the PIK3CA and DNA repair pathways as recurrent pathogenic alterations in TNBC...

BACKGROUND: Immunocheckpoint inhibitors (ICIs) have been widely used in the clinical treatment of lung cancer. Although clinical studies and trials have shown that patients can benefit significantly after PD-1/PD-L1 blocking therapy, less than 20% of patients can benefit from ICIs therapy due to tumor heterogeneity and the complexity of immune microenvironment. Several recent studies have explored the immunosuppression of PD-L1 expression and activity by post-translational regulation...

BACKGROUND: Neoadjuvant chemoradiotherapy (nCRT) is recommended as the preferred treatment for locally advanced esophageal squamous cell carcinoma. Recent studies have shown that immune checkpoint inhibitors are beneficial in treating advanced esophageal cancer. Therefore, a growing number of clinical centers are conducting trials of neoadjuvant immunotherapy or neoadjuvant immunotherapy plus chemotherapy (nICT) in patients with locally advanced resectable esophageal cancer. Immunocheckpoint inhibitors are expected to play a role in neoadjuvant therapy for esophageal cancer...