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Background: Immune checkpoint inhibitors (ICIs), including those targeting PD-1, are currently used in a wide range of tumors, but only 20-40% of patients achieve clinical benefit. The objective of our study was to find predictive peripheral blood-based biomarkers for ICI treatment., Methods: In 41 patients with advanced malignant melanoma (MM) and NSCLC treated with PD-1 inhibitors, we analyzed peripheral blood-based immune subsets by flow cytometry before treatment initialization and the second therapy dose. Specifically, we assessed basic blood differential count, overall T cells and their subgroups, B cells, and myeloid-derived suppressor cells (MDSC). In detail, CD4 + and CD8 + T cells were assessed according to their subtypes, such as central memory T cells (TCM), effector memory T cells (TEM), and naïve T cells (TN). Furthermore, we also evaluated the predictive value of CD28 and ICOS/CD278 co-expression on T cells., Results: Patients who achieved disease control on ICIs had a significantly lower baseline proportion of CD4 + TEM (p = 0.013) and tended to have a higher baseline proportion of CD4 + TCM (p = 0.059). ICI therapy-induced increase in Treg count (p = 0.012) and the proportion of CD4 + TN (p = 0.008) and CD28 + ICOS- T cells (p = 0.012) was associated with disease control. Patients with a high baseline proportion of CD4 + TCM and a low baseline proportion of CD4 + TEM showed significantly longer PFS (p = 0.011, HR 2.6 and p ˂ 0.001, HR 0.23, respectively) and longer OS (p = 0.002, HR 3.75 and p ˂ 0.001, HR 0.15, respectively). Before the second dose, the high proportion of CD28 + ICOS- T cells after ICI therapy initiation was significantly associated with prolonged PFS (p = 0.017, HR 2.51) and OS (p = 0.030, HR 2.69). Also, a high Treg count after 2 weeks of ICI treatment was associated with significantly prolonged PFS (p = 0.016, HR 2.33)., Conclusion: In summary, our findings suggest that CD4 + TEM and TCM baselines and an early increase in the Treg count induced by PD-1 inhibitors and the proportion of CD28 + ICOS- T cells may be useful in predicting the response in NSCLC and MM patients., Competing Interests: Declarations. Ethical approval: The study was conducted in accordance with the Declaration of Helsinki, and approved by the Institutional Review Board and Ethics Committee of Masaryk Memorial Cancer Institute, reference number 2017/1890/MOU; 27 June 2017. Consent to participate: Informed consent was obtained from all individual participants included in the study. Consent for publication: Not applicable. Competing interests: Dr. Borilova reported receiving personal fees from Bristol Myers Squibb and MSD outside the submitted work, Dr. Grell reported receiving personal fees from Bristol Myers Squibb, Roche and Servier outside the submitted work, Dr. Poprach reported receiving personal fees from Roche, Bristol Myers Squibb, Merck KGaA, MSD, Novartis, Astellas, Janssen, and Sanofi/Aventis, Ipsen, and Pfizer outside the submitted work. The other authors have no competing interests to declare that are relevant to the content of this article., (© 2024. The Author(s).)

Background: The aim of this retrospective study is to analyze a consecutive cohort of brain metastasis (BM) patients treated off clinical trials through combination of surgery and radiotherapy over the last 15 years in a tertiary neurooncology center., Materials and Methods: All BM patients operated between 2007-2019 received adjuvant linac-based radiotherapy categorized to whole brain radiotherapy (WBRT) and tumor bed stereotactic radiotherapy. Survival outcomes and local control was analyzed., Results: In total, 118 patients were enrolled, those with stereotactic radiotherapy (41%) had better baseline characteristics mirrored in longer overall survival (OS) [18 vs . 7.1 months, p < 0.001; hazard ratio (HR) 0.47, p = 0.004] with median follow-up of 58 months. Cumulative incidence for local, distant, and extracranial control was not significantly different between groups, with 12-month cumulative control of 22% vs . 18%, 44% vs . 29%, and 35% vs . 32% for stereotactic and WBRT group, respectively. WBRT was an independent factor for better distal brain control., Conclusions: Real world data demonstrating significantly better overall survival in patients treated with postoperative targeted radiotherapy compared with postoperative WBRT is presented, with no significant difference in cumulative incidence for local or distant brain control. The majority of patients with targeted radiotherapy had a fractionated dose schedule with outcomes comparable to single-dose radiation trials of postoperative targeted radiotherapy., Competing Interests: Conflicts of interest: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results., (© 2024 Greater Poland Cancer Centre.)

Background: Treatment options for metastatic renal cell carcinoma (mRCC) are rapidly expanding, and immunotherapy using checkpoint inhibitors is a first- or second-line option for most patients., Objective: The objective of the present retrospective analysis was to explore the real-world impact of checkpoint inhibitor-based immunotherapy compared with therapy using other types of targeted therapies using a large real-world database., Methods: RenIS, a registry of patients with mRCC was used as a data source. Outcomes were compared for cohorts treated with TKIs or mTOR inhibitors only [targeted therapy (TT) cohort] versus patients who received immunotherapy (IO) using a checkpoint inhibitor in any line of treatment (IO cohort). Data from a total of 1981 patients were extracted from the registry, including 1767 patients in the TT cohort and 214 patients in the IO cohort., Results: The median overall survival from the initiation of first-line treatment was 24.5 months versus not reached (p < 0.001) in the TT cohort versus the IO cohort, respectively [HR 0.23, 95% CI (0.17-0.31), p < 0.001]. The probability of 5-year survival was 24.2 versus 67.9% in the TT cohort versus the IO cohort, respectively. Immunotherapy in any line of treatment was associated with a lower risk of death. Overall survival was superior for patients receiving immunotherapy as the first or second treatment line compared with patients treated with non-immunological targeted therapy., Conclusion: In real-world patients with mRCC, immunotherapy is associated with significant survival benefit. The present retrospective analysis shows the real-world benefit of second-line immunotherapy in patients previously treated with tyrosine-kinase inhibitors., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Glioblastoma (GBM) is regarded as an aggressive brain tumor that rarely develops extracranial metastases. Despite well-investigated molecular alterations in GBM, there is a limited understanding of these associated with the metastatic potential. We herein present a case report of a 43-year-old woman with frontal GBM with primitive neuronal component who underwent gross total resection followed by chemoradiation. Five months after surgery, the patient was diagnosed with an intraspinal GBM metastasis. Next-generation sequencing analysis of both the primary and metastatic GBM tissues was performed using the Illumina TruSight Tumor 170 assay. The number of single nucleotide variants observed in the metastatic sample was more than two times higher. Mutations in TP53 , PTEN , and RB1 found in the primary and metastatic tissue samples indicated the mesenchymal molecular GBM subtype. Among others, there were two inactivating mutations (Arg1026Ile, Trp1831Ter) detected in the NF1 gene, two novel NOTCH3 variants of unknown significance predicted to be damaging (Pro1505Thr, Cys1099Tyr), one novel ARID1A variant of unknown significance (Arg1046Ser), and one gene fusion of unknown significance, EIF2B5-KIF5B , in the metastatic sample. Based on the literature evidence, the alterations of NF1 , NOTCH3 , and ARID1A could explain, at least in part, the acquired invasiveness and metastatic potential in this particular GBM case.

High-grade gliomas are primary brain tumors with poor prognosis, despite surgical treatment followed by radiotherapy and concomitant chemotherapy. We present two cases of long-term survival in patients treated for high-grade glioma and concomitant prolonged bacterial wound infection. The first patient treated for glioblastoma IDH-wildtype had been without disease progression for 61 months from the first resected recurrence. Despite incomplete chemotherapy-induced myelosuppression in the second patient with anaplastic astrocytoma IDH-mutant, she died without disease relapse after 14 years from the diagnosis due to other comorbidities. We assume that the documented prolonged survival could be related to the bacterial infection., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Solár, Mackerle, Hendrych, Pospisil, Lakomy, Valekova, Hermanova and Jancalek.)

Hematopoietic humanized (hu) mice are powerful tools for modeling the action of human immune system and are widely used for preclinical studies and drug discovery. However, generating a functional human T cell compartment in hu mice remains challenging, primarily due to the species-related differences between human and mouse thymus. While engrafting human fetal thymic tissues can support robust T cell development in hu mice, tissue scarcity and ethical concerns limit their wide use. Here, we describe the tissue engineering of human thymus organoids from inducible pluripotent stem cells (iPSC-thymus) that can support the de novo generation of a diverse population of functional human T cells. T cells of iPSC-thymus-engrafted hu mice could mediate both cellular and humoral immune responses, including mounting robust proinflammatory responses on T cell receptor engagement, inhibiting allogeneic tumor graft growth and facilitating efficient Ig class switching. Our findings indicate that hu mice engrafted with iPSC-thymus can serve as a new animal model to study human T cell-mediated immunity and accelerate the translation of findings from animal studies into the clinic., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

The 21st century is considered the age of malnutrition resulting in the unprecedented frequency of civilization diseases. Among these disorders, obesity is particularly distinguished and considered an epidemic-scale disease. For this reason, conducting studies on obesity and counteracting this phenomenon is essential. Research from recent years indicates a problem of excessive body weight among officers of uniformed services, who should be characterized by good health and fitness level due to the specificity of the work. As the problem of obesity affects every fourth Pole, research in uniformed services seems to be essential from health and national security perspectives. The presented study aimed to determine the elements of nutritional status in 289 students of Polish police schools and police training centers. Body composition was determined by bioelectrical impedance analysis, and bone calcification assessment was conducted by the DXA densitometric method. Based on BMI and body fat content, body weight disorders were found in 31.8% of all examined students. Densitometric test results showed changes in bone calcification of varying severity in 26.6% of the total number of respondents. The presence of obesity in students of police schools and training centers proves that the present nutrition model is energetically unbalanced, while the demonstrated disorders of bone calcification indicate an improper condition of mineral nutrition.