IL-2 is a pleiotropic cytokine that plays a central role in the activation and proliferation of cytotoxic lymphocytes and regulatory T cells. Since its discovery in 1976 as a T-cell growth factor and its subsequent U.S. FDA approval for metastatic renal cell carcinoma and melanoma, IL-2 has represented a landmark in cancer immunotherapy. However, high-dose (HD) IL-2 therapy is associated with substantial toxicities, including vascular leak syndrome. Recent advances in structural and receptor biology have clarified the molecular mechanisms underlying IL-2's dual immunostimulatory and immunoregulatory effects. These discoveries have enabled the design of next-generation IL-2 variants (IL-2v) with improved pharmacokinetics, receptor selectivity, and safety profiles. Importantly, PD-1⁺ TCF-1⁺ stem-like CD8⁺ T cells have recently been identified as a key population sustaining long-term antitumor immunity. TCF-1 is a transcription factor associated with a less differentiated, self-renewing state and marks this progenitor-exhausted subset. By contrast, terminally exhausted T cells exhibit a highly differentiated, poorly proliferative state and limited capacity for functional reinvigoration, whereas progenitor-exhausted cells retain stem-like properties, self-renewal capacity, and responsiveness to therapy. Furthermore, these cells respond robustly to IL-2 and are central mediators of the synergy observed between IL-2 signaling and PD-1 blockade. Mechanistically, PD-1 inhibition releases inhibitory constraints, while IL-2 provides a potent STAT5-driven proliferative and differentiation signal that expands the stem-like CD8⁺ T-cell pool and generates functional effector CD8⁺ T cells. This review summarizes IL-2 biology, the limitations of high-dose IL-2 (HD IL-2) therapy, and emerging strategies, including CD25- or CD122-biased IL-2 variants, tumor-targeted IL-2 prodrugs, and IL-2-based combination therapies designed to harness IL-2's antitumor potential while minimizing systemic toxicity, with particular emphasis on the role of stem-like CD8⁺ T cells as key mediators of therapeutic efficacy.

Erdheim-Chester disease (ECD) is a rare histiocytic neoplasm characterized by heterogeneous clinical manifestations and limited evidence to guide targeted therapy. While MEK inhibitors (MEKi) are increasingly used, data on their real-world efficacy, durability, and safety remain incomplete. We analyzed outcomes of patients with ECD treated with MEKi monotherapy across eight countries and assessed the dynamics and predictors of response, treatment retention, and the safety profile of MEKi. We included 170 patients and were able to evaluate response in 159 (94%) of them. Objective responses were observed in 112 patients (70%), disease stabilization in 35 (22%), and disease progression in 12 (8%). Response rates were independent of treatment lines and underlying molecular alterations. The median time to best response was 14 months, with an estimated 2-year probability of response of 61% (95% CI 51%-67%). In multivariable analysis, dyslipidemia (odds ratio [OR] 0.359, 95% CI 0.171-0.745) and neurodegeneration (OR 0.354, 95% CI 0.144-0.864) were associated with a lower probability of response to MEKi, while cutaneous and gastrointestinal involvement with a higher probability. After a median follow-up of 27 months (interquartile range [IQR] 12-57), the treatment retention rate was 76%, with most discontinuations attributable to toxicity. Adverse events were reported in 106 patients (62%) and were severe in 39 patients (23%). The estimated 2-year event-free survival was 65% (95% CI 57%-72%), and the estimated 2-year overall survival was 80% (95% CI 72%-86%). MEKi monotherapy provides robust and durable clinical efficacy in patients with ECD, with high response rates and favorable long-term outcomes, despite a substantial burden of toxicity.

Postoperative acute pain is a common challenge after breast cancer surgery. This randomized controlled trial compared the analgesic effects of ultrasound-guided erector spinae plane block (ESPB) and modified intercostal nerve block (MINB) in patients undergoing unilateral modified radical mastectomy.

Seventy patients were randomly allocated to ESPB or MINB group. The primary outcomes were the 6-hour postoperative resting and movement-evoked Visual Analogue Scale (VAS) scores. Secondary outcomes included resting and movement-evoked VAS scores at 0, 3, 12, and 24 hours, intraoperative opioid consumption, rescue analgesic use within 72 hours, Quality of Recovery-15 (QoR-15) score at 24 hours, and hospital stay.

At 6 hours postoperatively, both resting VAS (median 2 [0-2] vs 2 [2-3], P=0.005) and movement-evoked VAS (median 3 [2-4] vs 4 [3-4], P=0.015) were lower in the MINB group. Resting VAS scores at 0 and 3 hours were comparable between groups. Movement-evoked VAS scores were lower in the MINB group at all post-surgery time points (P<0.05 for all). Intraoperative remifentanil consumption was lower in the MINB group (P<0.001). Fewer patients required rescue analgesics in the MINB group (P=0.038). No significant difference was observed in QoR-15 scores between groups (P=0.055).

Ultrasound-guided MINB was associated with lower 6-hour resting and movement-evoked pain scores and reduced intraoperative opioid consumption compared with ESPB, without compromising recovery quality in patients undergoing unilateral modified radical mastectomy.

Chinese Clinical Trial Registry (ChiCTR2300077956; https://www.chictr.org.cn/showproj.aspx?proj=77956). Registered on November 24, 2023. Principal investigator: Guanghong Xu.

Prolactinomas account for approximately 30% to 50% of pituitary adenomas. Dopamine agonists (DAs) are the first-line treatment and effectively induce tumor regression while normalizing prolactin levels. However, DA therapy not only inhibits tumor growth but also is associated with fibrosis within the tumor. This fibrotic transformation remodels the tumor microenvironment (TME), altering cellular interactions, vascular structures, and extracellular matrix (ECM) composition. We hypothesize that this fibrotic response may not be a mere side effect; emerging, though largely indirect, evidence suggests it could potentially protect residual tumor cells by impeding drug penetration and facilitating immune evasion. Despite extensive clinical use of DAs, the mechanisms underlying DA-associated fibrosis and its implications for tumor behavior as well as patient outcomes remain poorly understood. This review integrates current knowledge regarding the pathophysiological processes leading to DA-associated fibrosis in prolactinomas, explores alterations in the TME, and assesses the clinical implications of these alterations. By integrating recent experimental and clinical studies, we aim to provide a comprehensive overview that elucidates the challenges posed by this fibrotic change in DA therapy and to propose actionable avenues for future research aimed at overcoming these obstacles.

To evaluate the occurrence of bladder malignancy or papillary urothelial neoplasm of low malignant potential (PUNLMP) detected at initial evaluation or during follow-up among adults with radiologically reported urachal anomalies, and to explore clinical factors associated with neoplasia.

We conducted a retrospective single-centre cohort study. Adult patients with radiologically reported urachal anomalies between 2000 and 2024 were identified through institutional radiology information system and report archive and underwent detailed chart review. Patients with a prior history of bladder or upper urinary tract malignancy were excluded. Clinical presentation, imaging findings, cystoscopy, histopathology and outcomes were analysed. Clinical variables associated with malignancy were explored using Firth penalized logistic regression.

A total of 245 patients were included: 92/245 (38%) had incidental/asymptomatic findings and 153/245 (62%) were symptomatic. Bladder malignancy/PUNLMP was detected in 14/245 patients (5.7%) overall, including 0/92 incidental/asymptomatic patients (0%) and 14/153 symptomatic patients (9.2%). Macroscopic haematuria was present in 12/14 patients with malignancy/PUNLMP and was associated with a higher frequency of neoplasia: 12/66 patients with haematuria (18%) versus 2/179 without haematuria (1%; p<0.001). In exploratory multivariable analysis, macroscopic haematuria remained associated with malignancy/PUNLMP (OR 5.29, 95% CI 1.10-39.5). Most detected tumours were of non-urachal histology, and 8/14 (57%) were stage T2 or higher.

Incidentally detected urachal anomalies in adults were not associated with malignancy during follow-up, suggesting that conservative management may be appropriate in asymptomatic patients. In contrast, symptomatic presentation, particularly macroscopic haematuria, warrants thorough urological evaluation due to its association with a substantially increased risk of bladder malignancy.

Prolactinomas are the most common functioning pituitary tumors in women of reproductive age and can affect fertility, gonadal and skeletal health, and vision. Management becomes particularly complex when reproductive plans intersect with diagnostic uncertainty, tumor anatomy, pregnancy-related enlargement, and long-term treatment decisions. This focused narrative Mini Review synthesizes current guidelines, consensus statements, systematic reviews, and clinically informative cohort studies and proposes a reproductive-intent-based framework for organizing individualized care. Adequate diagnostic confidence is required before pathway assignment; patients may then enter one of three proposed dynamic management states: fertility-driven, endocrine-stabilization, or surveillance-dominant. Tumor-related risk-including optic-apparatus proximity, documented growth, apoplexy, and clinically important dopamine agonist resistance or intolerance-acts as a cross-cutting safety modifier. Dopamine agonists remain first-line therapy for most patients, with surgery considered for selected anatomically favorable tumors or when medical treatment is ineffective or poorly tolerated. Preconception care aims to restore ovulation and establish anatomical safety; pregnancy surveillance is predominantly symptom-driven; and postpartum reassessment should precede treatment resumption. Persistent hyperprolactinemia alone does not necessarily justify therapy without clinically meaningful hypogonadism, symptoms, or tumor progression. In women not seeking pregnancy, treatment intensity should reflect gonadal status, symptoms, skeletal consequences, and tumor risk. This framework does not replace guideline-based recommendations or constitute a validated clinical classification; rather, it makes management priorities and transitions explicit and requires prospective validation.

The metabolic interface between tumor and immune cells is an emerging determinant of immunotherapy resistance, yet its therapeutic exploitation in hepatocellular carcinoma (HCC) remains limited. Adoptive cellular immunotherapies, including NK cell infusion, tumor-infiltrating lymphocytes (TILs), and chimeric antigen receptor T (CAR-T) cells, have transformed hematologic oncology but repeatedly fail to achieve durable responses in HCC. We argue that an underappreciated driver of this resistance is the acidic tumor microenvironment (TME): hypoxia-driven glycolytic reprogramming acidifies the HCC niche through lactate and proton accumulation, lowering extracellular pH (pHe) to approximately 6.5-6.8 (measured 6.66 ± 0.19 in human HCC by CEST MRI), rewiring macrophages, neutrophils, dendritic cells, NK cells, myeloid-derived suppressor cells, and T lymphocytes toward immunosuppressive or exhausted states. Although lactate and tumor acidity have each been reviewed extensively, the specific implications of acidosis for the design and delivery of cell-based therapies remain scattered and unsynthesized, a gap of growing urgency as the first pH-targeting and acidity-armored cellular products enter clinical testing, as summarized in this review. This mini review delineates how the acidic TME is established in HCC, summarizes cell-type-specific mechanisms of acidosis-driven immune dysfunction, and critically evaluates unresolved issues: the incomplete dissociation of acidity- versus lactate-mediated effects, the metabolic double-edged sword of systemic glycolytic blockade, and the gap between preclinical pH modulation and clinical translation. We conclude that ex vivo metabolic preconditioning and acidity-responsive cell engineering, rather than systemic metabolic intervention, offer the most tractable path toward durable cellular immunotherapy in HCC.

Innate immune signaling is a central regulator of cancer immunity, but its effects are highly context-dependent. Acute and spatially controlled innate immune activation can promote dendritic-cell maturation, antigen presentation, and cytotoxic lymphocyte recruitment. In contrast, chronic, systemic, or therapy-induced inflammatory signaling often redirects the tumor ecosystem toward suppressive myeloid remodeling. This review discusses how innate immune pathways reshape myelopoiesis, macrophage polarization, MDSC activation, tumor-associated neutrophil recruitment, and stromal-myeloid inflammatory niches. We focus on selected signaling axes that represent distinct layers of innate inflammatory regulation, including cytokine-mediated myeloid instruction, inflammasome activation, nucleic-acid sensing, chemokine-driven recruitment, stromal transcriptional integration, and lipid-mediator signaling. These axes include IL-4/IL-4Rα, IL-1α/IL-1β, TGF-β, interferon signaling, NLRP3 inflammasome activation, STING, STAT3, IL-8/CXCR2, CCR2, and CysLTR1. These pathways can expand suppressive myeloid output from the bone marrow, reinforce tumor-associated macrophage states such as TREM2⁺, SPP1⁺, and NLRP3⁺ macrophages, and promote MDSC- and neutrophil-mediated resistance to immune checkpoint blockade. We also summarize tissue, spatial, and peripheral biomarkers that may identify myeloid-dominant immune resistance. Finally, we discuss therapeutic strategies aimed at blocking inflammatory drivers, inhibiting inflammasome-dependent amplification, preventing suppressive myeloid recruitment, and reprogramming established myeloid niches. Rather than cataloguing individual myeloid subsets or isolated inflammatory pathways, this review integrates systemic myelopoiesis, local TAM/MDSC/TAN remodeling, stromal-myeloid spatial niches, and therapy-induced inflammatory feedback into a unified framework for understanding and targeting immune checkpoint blockade resistance.

It remains unclear whether preoperative patient-reported physical functioning (PF) correlates with postoperative wearable-measured physical activity in cancer patients. Clarifying this relationship could indicate whether brief self-report items capture information relevant to subsequent postoperative outpatient activity.

We analyzed 119 postoperative cancer patients from the SCRUM-MONSTAR LIFELOG study using four preoperative Medical Outcomes Study Short Form-36 (SF-36) PF items (stair climbing, vigorous activity, moderate activity, and carrying items; composite score 0-8), the Geriatric-8 (G8) screening tool, and wrist-based wearable accelerometry data. Spearman rank correlations, Wilcoxon rank-sum tests, and overlap-weighted analyses adjusted for clinical covariates were performed. Exploratory residual-based analyses examined the discordance between preoperative assessment and postoperative activity.

Patients with full PF (PF = 8; n = 53) versus impaired PF (PF < 8; n = 66) showed lower sedentary time (median 83.6% vs 87.3%; p = 0.031), higher moderate-to-vigorous physical activity (MVPA; 4.1% vs 2.7%; p = 0.015), and higher mean acceleration (21.8 vs 16.8 milligravity units; p = 0.044). All four SF-36 PF items showed consistent associations with sedentary time (Spearman ρ: -0.24 to -0.27) and MVPA (ρ: +0.23 to +0.29). G8-vulnerable patients showed higher sedentary time (87.2% vs 82.7%; p = 0.021) and lower MVPA (2.9% vs 4.1%; p = 0.045). After overlap-weighted adjustment, differences were attenuated. In exploratory analyses, age showed the most consistent, although weak, association with the discrepancy between preoperative assessment and postoperative activity.

The preoperative SF-36 PF items showed weak but consistent unadjusted associations with postoperative physical activity, although attenuated after adjustment for baseline clinical covariates. These findings suggest that brief preoperative self-report items may capture information relevant to subsequent physical activity behavior in cancer patients, with group-level differences partly reflecting shared clinical context.

Myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions are rare aggressive malignancies. FGFR1-rearranged cases are particularly high-risk. Among FGFR1 fusion partners, TIF1/TRIM24::FGFR1 is exceptionally rare. We report a 33-year-old woman presenting with fever, skin bruising, leukocytosis, thrombocytopenia, and circulating blasts. Bone marrow and flow cytometry identified abnormal B-lymphoblasts, myeloid blasts, and monocytic populations, supporting a mixed-phenotype acute leukemia presentation. Cytogenetics detected t(8;7)(p11;q34) translocation. Whole-transcriptome sequencing identified a TIF1/TRIM24::FGFR1 fusion transcript, confirmed by Sanger sequencing and FISH. RUNX1 missense mutation was also detected. The patient achieved complete remission after induction chemotherapy. However, after discontinuation of therapy and refusal of allo-HSCT, she relapsed rapidly with clonal evolution. A second remission was transient, and the patient died of cerebral hemorrhage. This case highlights the aggressive biology of TIF1/TRIM24::FGFR1-rearranged MLN-TK, the limitation of conventional chemotherapy, and the potential value of fusion-specific monitoring. Early allo-HSCT should be considered once remission is achieved, and FGFR1-directed therapy may represent a potential option in selected patients. However, clinical evidence remains limited and further studies are required.