The standard treatment of ovarian cancer (OC) patients, including debulking surgery and first-line chemotherapy, is unsatisfactory because of recurrent episodes in the majority (~70%) of patients with advanced OC. Clinical trials have shown only a modest (10–15%) response of OC individuals to treatment based on immune checkpoint inhibitors (ICIs). The resistance of OC to therapy is caused by various factors, including OC heterogeneity, low density of tumor-infiltrating lymphocytes (TILs), non-cellular and cellular interactions in the tumor microenvironment (TME), as well as a network of microRNA regulating immune checkpoint pathways. Moreover, ICIs are the most efficient in tumors that are marked by high microsatellite instability and high tumor mutation burden, which is rare among OC patients. The great challenge in ICI implementation is connected with distinguishing hyper-, pseudo-, and real progression of the disease. The understanding of the immunological, molecular, and genetic mechanisms of OC resistance is crucial to selecting the group of OC individuals in whom personalized treatment would be beneficial. In this review, we summarize current knowledge about the selected factors inducing OC resistance and discuss the future directions of ICI-based immunotherapy development for OC patients.
Non-small cell lung cancer (NSCLC) is the most common type of lung cancer and the leading cause of cancer-related mortality worldwide. It is responsible for 80–85% of lung cancer cases. NSCLC can be divided into several groups, led by adenocarcinoma (ADC)–40–50% and squamous cell carcinoma (SCC)–20–30%. The development of new molecular therapies targeting particular abnormalities such as mutations in the EGFR (Epidermal Growth Factor Receptor) gene or ROS1 or ALK genes rearrangements resolved in novel strategies in advanced NSCLC management. EGFR mutation occurs mostly in patients with ADC and those patients are mostly females with no or light smoking history. The hereby presented patient fitted the ADC characteristics, while they were diagnosed with SCC. The unusual diagnosis implied further genetic testing, which established the occurrence of L858R substitution in exon 21 in the EGFR gene. A 63-year-old female was admitted to the unit due to a dry cough, pain in the right chest area and dyspnoea. When diagnosed, the patient had a peripheral mass in the right lung superior lobe (55 × 40 mm), satellite nodules in the apex of the same lung and packets of disintegrating lymph nodes. Positron Emission Tomography (PET-CT) confirmed a diffuse neoplastic process qualified as stage IV on the TNM scale. Due to EGFR gene mutation, the woman was administered osimertinib, however, the treatment did not succeed, and other therapeutic solutions were undertaken. The patient died 10 months after diagnosis. Patients with advanced ADC harboring EGFR mutation can receive osimertinib, a third-generation tyrosine kinase inhibitor (TKI), however, the use of TKIs in SCC remains controversial. In some published cases, osimertinib treatment led to success, in others, the therapy did not result in the expected final effect. Small sample groups and diverse molecular backgrounds indicate the need for further research in this field. Thus, the treatment decision-making process in those patients overall remains extremely demanding and ambiguous.
Pregnant women with obesity and diabetes are at increased risk of developing infections and other complications during pregnancy. Several mechanisms are involved in the immunological mechanisms that contribute to reduced immunity in these populations. Both obesity and diabetes are associated with chronic low-grade inflammation that can lead to an overactive immune response. Pregnant women with obesity and diabetes often have an increase in pro-inflammatory cytokines and adipokines, such as TNF-α, IL-6, IL-1β, leptin, and resistin, which are involved in the inflammatory response. Insulin resistance can also affect the functioning of immune cells. Furthermore, both conditions alter the composition of the gut microbiome, which produces a variety of biomolecules, including short-chain fatty acids, lipopolysaccharides, and other metabolites. These substances may contribute to immune dysfunction. In addition to increasing the risk of infections, obesity and diabetes can also affect the efficacy of vaccinations in pregnant women. Pregnant women with obesity and diabetes are at increased risk of developing severe illness and complications from COVID-19, but COVID-19 vaccination may help protect them and their fetuses from infection and its associated risks. Since both obesity and diabetes classify a pregnancy as high risk, it is important to elucidate the impact of these diseases on immunity and vaccination during pregnancy. Research examining the efficacy of the COVID-19 vaccine in a high-risk pregnant population should be of particular value to obstetricians whose patients are hesitant to vaccinate during pregnancy. Further research is needed to better understand these mechanisms and to develop effective interventions to improve immune function in these populations.
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