Introduction: Chimeric Antigen Receptor (CAR)-T cell therapy is a form of adoptive cell therapy that has demonstrated tremendous results in the treatment of hematopoietic malignancies, leading to the US Food and Drug Administration (FDA) approval of four CD19-targeted CAR-T cell products. With the unprecedented success of CAR-T cell therapy in hematological malignancies, hundreds of preclinical studies and clinical trials are currently undergoing to explore the translation of this treatment to solid tumors. However, the clinical experience in non-hematologic malignancies has been less encouraging, with only a few patients achieving complete responses. Tumor-associated antigen heterogeneity, inefficient CAR-T cell trafficking and the immunosuppressive tumor microenvironment are considered as the most pivotal roadblocks in solid tumor CAR-T cell therapy. Materials and methods: We reviewed the relevant literature/clinical trials for CAR-T cell immunotherapy for solid tumors from Pubmed and ClinicalTrials.gov. Conclusion: Herein, we provide an update on solid tumor CAR-T cell clinical trials, focusing on the studies with published results. We further discuss some of the key hurdles that CAR-T cell therapy is encountering for solid tumor treatment as well as the strategies that are exploited to overcome these obstacles.

The expression of estrogen receptors (ERs) in breast cancer (BC) represents a strong prognostic and predictive biomarker and directs therapeutic decisions in early and advanced stages. ER-low-positive BC, defined by the immunohistochemical (IHC) expression of ERs from 1% to 9%, constitutes a distinct subset of total BC cases. Guidelines recommend that a low expression of ERs be reported in pathology reports since the benefit of endocrine therapy in patients with ER-low-positive BC is uncertain. Recently, several cohorts, mostly of a retrospective nature, have been published, reporting the clinicopathological characteristics and outcomes of ER-low-positive BC. However, the majority of the data focus on early-stage BC and the use of (neo)adjuvant therapy, and there is a significant lack of data regarding metastatic ER-low-positive BC. Further factors, including tumor heterogeneity as well as the potential loss of ER expression due to endocrine resistance, should be considered. Including patients with ER-low-positive BC in clinical trials for triple-negative breast cancer (TNBC) might improve the understanding of this entity and allow novel therapeutic approaches. The design and conduction of randomized clinical trials regarding this subgroup of patients are greatly anticipated.

STING-associated vasculopathy with onset in infancy (SAVI) is a rare type Ι interferonopathy caused by gain of function mutations in an encoding stimulator of interferon genes (STING) protein 1. SAVI is characterized by neonatal or infantile-onset systemic inflammation, mainly affecting peripheral cutaneous blood vessels, skin, and lungs. The main disease manifestations include recurrent febrile episodes, cough, dyspnea, and failure to thrive, in association with progressive interstitial lung disease, polyarthritis, and cold-induced red violet plaques or papules on fingers, knees, toes, heels, nasal tip, and ears that can lead to distal ulcerations, skin necrosis, tissue loss, and autoamputation. For the management of SAVI, JAK inhibitors can be a valuable therapeutic intervention that hampers disease progression, while conventional immunosuppressive treatments have shown minimal efficacy. This review aims to describe the underlying pathophysiologic mechanisms of SAVI, highlighting the main clinical manifestations and discussing the current treatment approaches.

Objective: To evaluate temporal trends in pregnancy management and outcomes in women with SLE and explore the impact of pregnancy planning on maternal and foetal complications. Methods: We conducted a retrospective study including women with SLE with one or more pregnancies after diagnosis or diagnosed during pregnancy. Data were collected through questionnaires and medical records. To assess temporal trends, the study period (1985–2024) was divided into five intervals with similar pregnancy and patient distribution. Using generalized estimating equations, we identified risk factors for adverse pregnancy outcomes and evaluated temporal trends in pregnancy characteristics. Results: We recorded 109 pregnancies from 65 women; 70.6% resulted in live births. Planned pregnancies were associated with a lower flare risk [odds ratio (OR) 0.31 (95% CI 0.11, 0.89)] and a higher likelihood of live birth [OR 3.31 (95% CI 1.41, 7.8)]. HCQ use during pregnancy was independently associated with a reduced flare risk [OR 0.26 (95% CI 0.08, 0.8)]. Pregnancies before 2005 were less often planned [OR 0.10 (95% CI 0.03, 0.4)], while HCQ use during pregnancy increased over time [OR 0.56 (95% CI 0.34, 0.95), for the period 1985–2005 vs 2021–2024], with discontinuation decreasing from 33% to <2%. The predicted probability of preventive aspirin use in patients without antiphospholipid syndrome increased from 12% before 2005 to 46% in 2021–2024, whereas continuous glucocorticoid use decreased from 58% before 2005 to 16% after 2020. The probability of foetal complications showed a decreasing trend after 2016. Conclusion: Pregnancy management and outcomes improved over time in SLE; planned pregnancy and HCQ use were associated with favourable results.

Objectives: Lupus Low Disease Activity State (LLDAS) and Definition of Remission in SLE (DORIS) are associated with improved outcomes in SLE; however, their value in lupus nephritis (LN) remains unexplored. We sought to evaluate their prognostic value on organ damage accrual, renal flares and chronic kidney disease in patients with LN. Methods: Multicentre retrospective cohort study of patients with biopsy-proven LN who achieved renal response. Enrolment date was the time of first renal response. Longitudinal data were analysed using Cox proportional hazards models. Modified LLDAS (mLLDAS) and DORIS (mDORIS) attainment and sustained durations were evaluated. Results: 155 patients with 1703 visits were included. During a median follow-up of 3.5 years (IQR 4.5), 127 patients (81.9%) achieved mLLDAS and 92 (59.4%) achieved mDORIS. Both states demonstrated robust protective effects across all outcomes. For organ damage, mLLDAS attainment was associated with 85% risk reduction (adjusted HR (aHR 0.15, 95% CI 0.07 to 0.32), while mDORIS conferred a 79% reduction (aHR 0.21, 95% CI 0.08 to 0.55). Periods under mLLDAS were also associated with a 73% reduction in renal flare risk (aHR 0.27, 95% CI 0.14 to 0.51), with similar effects for mDORIS. Sustained achievement resulted in progressively greater protection, with the strongest effects seen for ≥24 consecutive months. Early attainment protected against damage accrual (aHR 0.31, 95% CI 0.16 to 0.61) and renal flares (aHR 0.51, 95% CI 0.29 to 1.00). Conclusions: Following renal response, achievement of mLLDAS and mDORIS is strongly associated with improved outcomes in LN patients. Earlier attainment and longer duration in these states confer progressively greater protection.

Background: Long COVID—defined as the persistence of symptoms or the development of new symptoms beyond four weeks after acute SARS-CoV-2 infection—affects an estimated 10–30% of individuals recovering from COVID-19, posing a significant public health burden. Emerging evidence suggests that type I interferons (IFNs) (a critical group of cytokines in the antiviral defense) and hematologic alterations, such as lymphopenia and elevated inflammatory markers, are linked to both the severity of acute COVID-19 and the likelihood of developing long-term symptoms. The aim of this study is to explore the association between type I IFN signatures and long COVID. A second aim is to examine the relationship between laboratory findings during acute infection and long COVID. Methods: The study included 61 patients investigated for the presence of long COVID symptoms 16.5 ±1.5 months after acute infection. Patients were divided into two groups of higher symptom burden of long COVID and those with milder symptoms based on demographic, laboratory, and clinical data as well as type I IFN-inducible gene expression (MX-1, IFIT-1, and IFI-44) measured in peripheral blood by real-time PCR. Data collected during acute infection were recorded. Peripheral blood samples were collected during the acute phase of infection, within the first 48 h of hospital admission. IFN-inducible gene expression was measured prospectively at that time, and RNA was extracted immediately for subsequent analysis. Results: History of intubation emerged as a significant associated factor of severe long COVID, with 75% of intubated patients reporting >8 persistent symptoms approximately 16 months post-infection. Higher white blood cell (WBC) and neutrophil counts but lower eosinophil and monocyte counts in acute infection were found to be associated with a high burden of long COVID symptoms. Interestingly, absolute monocyte count was found to independently correlate with higher long COVID symptom burden. Lactate dehydrogenase (LDH) and serum glutamic-oxaloacetic transaminase (SGOT) also differed significantly between groups, with higher levels correlating with a high burden of long COVID symptoms. Notably, MX-1 transcript levels in peripheral blood at the time of acute infection were reduced in patients with a high burden of long COVID symptoms, suggesting that dysregulated immune responses during the acute phase may contribute to persistent symptoms. Conclusions: These findings suggest the potential association of hematological and immune markers with long COVID severity, as well as the importance of monitoring these parameters to identify at-risk patients for early interventions.