Introduction: Identification of modulators of the immune response with inhibitory properties that could be susceptible for therapeutic intervention is a key goal in cancer research. An example is the human leukocyte antigen G (HLA-G), a nonclassical major histocompatibility complex (MHC) class I molecule, involved in cancer progression. Methods: In this article we performed a systematic review and meta-analysis on the association between HLA-G expression and outcome in solid tumors. This study was performed in accordance with PRISMA guidelines and registered in PROSPERO.Results: A total of 25 studies met the inclusion criteria. These studies comprised data from 4871 patients reporting overall survival (OS), and 961 patients, reporting disease free survival (DFS). HLA-G expression was associated with worse OS (HR 2.09, 95% CI = 1.67 to 2.63; P < .001), that was higher in gastric (HR = 3.40; 95% CI = 1.64 to 7.03), pancreatic (HR = 1.72; 95% CI = 0.79 to 3.74) and colorectal (HR = 1.55; 95% CI = 1.16 to 2.07) cancer. No significant differences were observed between the most commonly utilized antibody (4H84) and other methods of detection. HLA-G expression was associated with DFS which approached but did not meet statistical significance. Discussion: In summary, we describe the first meta-analysis associating HLA-G expression and worse survival in a variety of solid tumors. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022311973.

Introduction: Evidence is scant regarding the long-term humoral and cellular responses Q7 triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccines in cancer patients after repeated booster doses. The possibility of T-cell exhaustion following these booster doses in this population has not yet been fully studied and remains uncertain.Methods: In this single-center prospective observational study, we explored the specific humoral and cellular response to S1 antigen in 36 patients with solid malignancies at baseline, and after the second and third doses of the mRNA-1273 vaccine.Results: A dual behavior was observed: 24 (66.7%) patients showed partial specific IFN-γ response after the second dose that was further enhanced after the third dose; and 11 (30.5%) already showed an optimal response after the second dose and experienced a marked fall-off of specific IFN-γ production after the third (4 patients negativization), which might suggest T cell exhaustion due to repetitive priming to the same antigen. One (2.8%) patient had persistently negative responses after all three doses. Seroconversion occurred in all patients after the second dose. We then studied circulating exhausted CD8+ T-cells in 4 patients from each of the two response patterns, those with increase and those with decrease in cellular response after the third booster. The patients with decreased cellular response after the booster had a higher expression of PD1⁺CD8⁺ and CD57⁺PD1⁺CD8⁺ exhausted T cells compared with those with an increased cellular response both in vivo and in vitro. The proportion of PD1⁺CD8⁺ and CD57⁺PD1⁺CD8⁺ exhausted T cells inversely correlated with IFN-γ production.Discussion: Our preliminary data show that the two-dose SARS-CoV-2 vaccine regimen was beneficial in all cancer patients of our study. An additional booster seems to be beneficial in suboptimal vaccine seroconverters, in contrast to maximal responders that might develop exhaustion. Our data should be interpreted with caution given the small sample size and highlight the urgent need to validate our results in other independent and larger cohorts. Altogether, our data support the relevance of immunological functional studies to personalize preventive and treatment decisions in cancer patients.

Background: Immunotherapy has gained momentum with the discovery of novel antibodies targeting immunosuppressive proteins. HLA-E, a non-classical major histocompatibility complex class I (MHC-I) protein, exhibits immunosuppressive properties, potentially influencing tumor immune evasion mechanisms. The association between Human Leukocyte Antigen E (HLA-E) expression and outcomes in solid tumors remains unclear.Methods: A systematic review of MEDLINE, Scopus, and the Cochrane Library up to March 15, 2024, was conducted following the PRISMA guidelines. Studies investigating HLA-E expression in solid tumors and its association with OS and DFS were included. Statistical analysis was performed using Comprehensive Meta-Analysis (version 3.0) with random-effects models.Results: After screening 657 articles, 11 studies were included, comprising a total of 1781 patients. The studies encompassed a variety of cancer types, follow-up periods, and staging details, with the majority focusing on non-metastatic cases. Notably, three studies evaluated colorectal cancer, while others focused on pancreatic, esophageal, brain, renal cell, gastric, endometrial, cervical, and hepatocellular carcinomas. The mean age of the patients was 59.81 ± 2.01 years, and the median follow-up period was 57.45 ± 8.91 months. HLA-E expression demonstrated no statistically significant association with OS (HR 0.913, 95% CI = 0.567-1.469; P=0.707), with significant heterogeneity observed (I2 = 84%). However, HLA-E non-expression was significantly associated with improved DFS (HR 1.406, 95% CI = 1.027-1.930; P=0.03), with moderate heterogeneity (I2 = 45%).Conclusion: This systematic review highlights that HLA-E expression in solid tumors could be a biomarker of better prognosis, measured by DFS. These findings align with the clinical benefit observed for agents targeting this pathway. However, further studies should be performed to confirm these preliminary observations.Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024527598, identifier CRD42024527598.

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Malignant pericardial mesothelioma (MPeM) is exceptionally rare, and its association with long‐standing idiopathic pericarditis remains unreported. We present a 46‐year‐old woman with a decade‐long history of recurrent idiopathic pericarditis who developed multiple pericardial nodules, mediastinal lymphadenopathy, and metastatic liver and bone lesions. A core needle biopsy confirmed biphasic MPeM. Due to her pericardial condition, she initially received platinum‐based chemotherapy instead of immunotherapy, but the disease progressed. She then underwent dual immune checkpoint inhibition (ICI) and achieved a significant clinical and radiological response. This case raises the possibility of chronic inflammation contributing to pericardial malignancy and underscores the potential role of dual ICI in this rare and challenging disease.