Malignant peritoneal mesothelioma (MPM) is a highly aggressive peritoneal malignancy with a significant recurrence rate following cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC). There is an urgent need to investigate novel therapeutic strategies for MPM. Natural killer (NK) cells exhibit rapid responsiveness in anti-tumor immunity; however, NK cells' dynamic evolution and clinical significance in MPM remain unclear.
This study retrospectively enrolled 80 newly diagnosed MPM patients (preoperative group) and 64 patients who underwent CRS + HIPEC (postoperative group). The level of NK cells (CD3-CD56dimCD16+) in peripheral blood was quantified using flow cytometry. Univariate and multivariate regression analyses were performed to evaluate the association between NK cell counts and clinicopathological characteristics, intraoperative events, and prognosis. A multivariate prediction model for NK cell recovery was established.
41 patients (51.3%) exhibited decreased NK cell levels preoperatively, which were significantly associated with an increased risk of thrombosis (P = 0.023), intraoperative plasma transfusion (P = 0.004), and prolonged hospitalization duration (P = 0.023). Postoperative dynamic changes in NK cell levels were found to correlate with Karnofsky performance scale (KPS) scores (P = 0.048) and elevated levels of IL-4, IL-5, IL-6, and IL-8 (P < 0.05). Multivariate analysis revealed that the volume of intraoperative plasma transfusion was an independent correlated factor for preoperative NK cell reduction (P = 0.013), while a low KPS score was an independent predictor of postoperative NK cell decline (P = 0.048). Survival analysis indicated that a high perioperative stress score (PSS) (P = 0.015), lymph node metastasis (P = 0.015), significant intraoperative blood loss (P = 0.013), low preoperative CD8⁺ T cell levels (P = 0.001), and reduced postoperative IL-17 expression (P = 0.013) were independent adverse prognostic factors for overall survival (OS). Furthermore, the dynamic NK cell recovery model demonstrated that baseline NK cell levels, peritoneal cancer index (PCI), CD8⁺ T cell status, and postoperative recovery time all significantly influenced the immune remodeling process (all P < 0.001).
Preoperative NK depletion correlated with thrombosis and surgical risks, while postoperative NK recovery was influenced by KPS, specific cytokines (IL-4/5/6/8), and was significantly enhanced after CRS + HIPEC.
© 2025. The Author(s).

The liquid biopsy (LB) represents a minimally invasive method for cancer screening that has been introduced in clinical practice for over a decade and that can accelerate treatment response assessment. LB allows the analysis of tumor cells or tumor-derived products (e.g. cell-free circulating nucleic acids, extracellular vesicles, and proteins) released from primary or metastatic tumor lesions into blood or other body fluids. In the era of immune-oncology, recent evidence indicates that tumor-specific immune responses can be detected in peripheral immune cells. The improvement of knowledge and the standardization of the isolation methods of these techniques will allow the detection and characterization of circulating tumor and immune biomarkers at an early stage as innovative tools to predict response to therapies. Nowadays, the analysis of peripheral blood mononuclear cells (PBMCs), circulating tumor cells (CTCs), peripheral blood-derived extracellular vesicles (EVs) and circulating tumor RNA (ctRNA) remains under-developed even if these non-invasive techniques can provide the complete genetic landscape of tumors and allow systematic tracking of cancer evolution. In addition, the evaluation of blood circulating cytokines, and early dynamics changes in the PBMCs of patients with solid tumors represent a promising area of research. Here, we present a comprehensive methodological framework for the evaluation of innovative peripheral blood-derived biomarkers. We also address the current challenges in isolation methods and analysis of PBMC, CTC, EVs and TEPs which are crucial for structuring the large amount of comprehensive information obtained from such samples, with the aim of advancing the translational cancer field.
© 2025 The Authors.

Malignant peritoneal mesothelioma (MPM) is a rare primary malignant tumor with an extremely poor prognosis that currently lacks effective treatment options. This study investigated the in vitro and in vivo efficacy of natural killer (NK) cells for treatment of MPM.
An in vitro study was conducted to assess the cytotoxicity of NK cells from umbilical cord blood to MPM cells with the use of a high-content imaging analysis system, the Cell Counting Kit-8 assay, and Wright-Giemsa staining. The level of NK cell effector molecule expression was detected by flow cytometry and enzyme-linked immunosorbent assays. The ability of NK cells to kill MPM cells was determined based on live cell imaging, transmission electron microscopy, and scanning electron microscopy. An in vivo study was conducted to assess the efficacy and safety of NK cell therapy based on the experimental peritoneal cancer index, small animal magnetic resonance imaging, and conventional histopathologic, cytologic, and hematologic studies.
NK cells effectively killed MPM cells through the release of effector molecules (granzyme B, perforin, interferon-γ, and tumor necrosis factor-α) in a dose- and density-dependent manner. The NK cell killing process potentially involved four dynamic steps: chemotaxis; hitting; adhesion; and penetration. NK cells significantly reduced the tumor burden, diminished ascites production, and extended survival with no significant hematologic toxicity or organ damage in NOG mice.
NK cell immunotherapy inhibited proliferation of MPM cells in vitro and in vivo with a good safety profile.
Copyright © 2024 The Authors.

The 5-year survival rate of patients with advanced non-small cell lung cancer (NSCLC) remains low, despite recent advances in targeted therapy and immunotherapy. Therefore, there is a need to identify alternative strategies to improve treatment outcomes. Modern diagnostics can significantly facilitate the selection of treatment plans to improve patient outcomes. In the present study, multi-form diagnostic methodologies were adopted, including next-generation sequencing-based actionable gene sequencing, programmed death ligand 1 (PD-L1) immunohistochemistry, a circulating tumor cell (CTC) assay, flow cytometric analysis of lymphocyte subsets and computed tomography, to improve disease management in an 86-year-old female patient with relapsed metastatic NSCLC. High expression of PD-L1, elevated CTC tmutations, were observed. Based on these results, the patient was initially treated with the programmed death protein 1 blocking antibody sintilimab for two cycles, resulting in the stabilization of their condition, although the patient still exhibited severe pain and other symptoms, including fatigue, malaise, a loss of appetite and poor mental state. Informed by dynamic monitoring of the patient's response to treatment, the treatment plan was subsequently adjusted to a combination therapy with sintilimab and autologous cytokine-induced killer cell infusion, which eventually led to improved outcomes in both the management of the cancer and quality of life. In conclusion, multi-omics analysis may be used to establish patient-tailored therapies to improve clinical outcomes in hard-to-treat elderly patients with metastatic NSCLC.
Copyright: © 2024 Xing et al.

Assessment of cellular immunity to the SARS-CoV-2 coronavirus is of great interest in chronically immunosuppressed transplant recipients (Tr), who are predisposed to infections and vaccination failures. We evaluated CD154-expressing T-cells induced by spike (S) antigenic peptides in 204 subjects-103 COVID-19 patients and 101 healthy unexposed subjects. S-reactive CD154+T-cell frequencies were a) higher in 42 healthy unexposed Tr who were sampled pre-pandemic, compared with healthy NT (p=0.02), b) lower in Tr COVID-19 patients compared with healthy Tr (p<0.0001) and were accompanied by lower S-reactive B-cell frequencies (p<0.05), c) lower in Tr with severe COVID-19 (p<0.0001), or COVID-19 requiring hospitalization (p<0.05), compared with healthy Tr. Among Tr with COVID-19, cytomegalovirus co-infection occurred in 34%; further, incidence of anti-receptor-binding-domain IgG (p=0.011) was lower compared with NT COVID-19 patients. Healthy unexposed Tr exhibit pre-existing T-cell immunity to SARS-CoV-2. COVID-19 impairs anti-S T-cell and antibody and predisposes to CMV co-infection in transplant recipients.