Anticancer therapy can eliminate immune-visible tumour cells while simultaneously imposing selective pressures that favour residual immune-evasive populations. This mini-review conceptualizes therapy-induced immunoediting as a dynamic continuum comprising pre-existing escape, therapeutic immune activation, a selective bottleneck, residual equilibrium and secondary escape. We discuss how genetic alterations, therapy-resistant stem-like tumour-cell states and spatial remodelling of vascular, stromal and myeloid niches cooperate to reduce tumour visibility, effector susceptibility and immune-cell access. Representative approved and investigational therapies illustrate both successful pharmacological interception and the limitations of non-selective immune intensification. We further highlight residual equilibrium as a clinically actionable window that may be identified through longitudinal tissue sampling, circulating tumour DNA and spatial or single-cell profiling. Clinically, longitudinal biomarkers may identify residual equilibrium and guide mechanism-matched treatment adaptation before immune-evasive populations expand into radiographically evident relapse.

Myelodysplastic syndrome (MDS) are clonal myeloid neoplasms that cause cytopenias and can progress to acute myeloid leukemia (AML). Hypomethylating agents (HMA) are the mainstay of treatment for higher risk disease, but they achieve responses in only half of treated patients and complete remission rates are low. Several scientifically based combinatorial regimens have been tested in clinical trials but none has demonstrated a survival benefit over HMA monotherapy. Allogeneic stem cell transplant remains the only curative therapy and is dependent on effective donor lymphocytes for its efficacy. However, access is limited by its toxicity, so alternative approaches are sorely needed. Recent clinical and translational studies have shown that MDS is not only a clonal myeloid disorder, but also associated with immune dysregulation, inflammatory signaling, T-cell repertoire restriction, immune exhaustion, and immune mediated suppression of hematopoiesis. These findings suggest that there is potential for unlocking a novel approach to the treatment of MDS by restoring and/or enhancing the lymphoid immune response. In this review, we discuss the current understanding of the role of normal T lymphocytes in MDS, the causes and manifestations of dysfunctional T lymphocytes as well as the role and dysfunction of natural killer (NK) cells. The role of therapeutic immunosuppression in lower risk MDS is reviewed, as is the impact of HMAs on dysregulated T lymphocytes and NK cells in higher risk disease. We propose that there is tremendous potential for more targeted approaches to engage the lymphoid compartment in addressing the unmet therapeutic need in MDS.

Stromal tumor-infiltrating lymphocytes (TILs) are established biomarkers in triple-negative breast cancer (TNBC), but conventional density-based assessment does not capture their spatial relationship to tumor nests. We evaluated whether an H&E-derived spatial architecture index (SAI) provides predictive information beyond stromal TIL density for pathologic complete response (pCR) after neoadjuvant therapy.

This single-center retrospective cohort included 236 patients with TNBC who had evaluable pretreatment core biopsy slides and definitive surgical response assessment. The primary SAI was the equally weighted mean of standardized close interaction ratio and lymphocyte cluster index, together with reverse-coded standardized lymphocyte-tumor distance and edge enrichment. The primary multivariable analysis included 231 patients with complete clinicopathologic data. Robustness was evaluated using bootstrap optimism correction, alternative SAI constructions, treatment-regimen and propensity-score analyses, repeated nested cross-validation, and a 60-case reproducibility assessment. During internal validation, preprocessing and SAI construction were repeated within each training fold.

Of 236 patients, 122 (51.7%) achieved pCR. In the main multivariable model, the SAI remained associated with pCR (OR 2.79 per 1 SD, 95% CI 1.79-4.35; P < 0.001), whereas stromal TIL density was not independently significant (OR 0.88 per 10% increase, 95% CI 0.74-1.04; P = 0.123). Bootstrap optimism-corrected AUROCs were 0.698 for the clinical model, 0.705 after the addition of stromal TIL density, 0.764 after the addition of the SAI, and 0.765 after the addition of both. Across six internally validated algorithms using the full feature set, mean AUROCs ranged from 0.730 to 0.752, with only modest between-algorithm differences. The SAI showed excellent interobserver reproducibility (ICC 0.93, 95% CI 0.89-0.95). Its association with pCR persisted in the chemotherapy-only subgroup (OR 2.48, 95% CI 1.52-4.05; P < 0.001), whereas the interaction with pembrolizumab-containing treatment was not significant (P = 0.222).

In this exploratory single-center retrospective cohort, the H&E-derived SAI provided internally validated predictive information beyond stromal TIL density for pCR. External multicenter validation, assessment of intersite technical reproducibility, and prospective calibration are required before clinical implementation.

Seborrheic keratosis (SK) is a common benign epidermal neoplasm, particularly affecting the elderly. Although non-malignant, it often poses cosmetic and diagnostic challenges due to its resemblance to malignant skin tumors. This review aims to provide a comprehensive update on the recent advancements in the epidemiology, pathogenesis, diagnostic modalities, and therapeutic approaches for SK.

A narrative review of current literature was conducted, focusing on molecular insights, diagnostic innovations, and therapeutic options for SK. Sources were identified through searches in PubMed, ScienceDirect, and Google Scholar over the last decade using relevant keywords.

Molecular research has highlighted the role of oncogenic mutations, including AKT pathway alterations and amyloid precursor protein (APP) involvement. Non-invasive diagnostic tools such as dermatoscopy, reflectance confocal microscopy (RCM), and optical coherence tomography (OCT) have improved lesion differentiation. Artificial intelligence (AI)-based algorithms have further enhanced diagnostic precision. While conventional therapies such as cryotherapy, excision, electrodesiccation, and laser remain effective, they may cause post-inflammatory hypopigmentation. Recent non-invasive treatments, including 30%-50% aqueous nitric-zinc oxide solution with organic acids, 65 or 80% trichloroacetic acid (TCA) solution, and 0.3% Annona muricata L. seed extract cream have demonstrated efficacy with minimal side effects. Nano-Pulse Stimulation (NPS) technology emerges as a novel low-complication treatment.

Advances in molecular understanding and technology have transformed the diagnostic and therapeutic landscape for SK. There is a growing need for accessible, effective, and cosmetically favorable treatment options, especially with rising patient demand. Further research is warranted to validate long-term efficacy and broaden availability.

Hepatocellular carcinoma (HCC) develops in a chronically injured liver where metabolic adaptation, oxidative stress, innate immune signalling, and immune tolerance are already intertwined. Mitochondria connect these processes: they sustain tumour-cell fitness, yet damaged organelles expose mitochondrial DNA (mtDNA) as an intracellular and intercellular danger signal. Persistent reactive oxygen species, altered mitochondrial dynamics, nucleoid instability, and incomplete mitophagy-lysosomal clearance can oxidise, fragment, and displace mtDNA. The resulting material may remain in the cytosol, circulate freely or in protein-associated complexes, or be transferred within extracellular vesicles. These forms are not immunologically equivalent. Cytosolic mtDNA favours cGAS-STING access; endocytosed material can engage endolysosomal TLR9; and oxidised mtDNA can cooperate with mitochondrial reactive oxygen species, ATP, cardiolipin, and ionic perturbation in NLRP3 inflammasome-associated signalling. Redox remodelling also alters interferon responsiveness, inflammasome competence, and myeloid-cell metabolism, allowing recipient cells to assign different meanings to a similar mitochondrial signal. We integrate these mechanisms into an acute immune activation-chronic immune adaptation continuum. Transient, spatially restricted, and efficiently cleared danger can support antigen presentation and effector recruitment, whereas recurrent or poorly cleared signalling can become embedded in suppressive myeloid remodelling, lymphocyte dysfunction, and spatial immune escape. Direct HCC studies support treatment-induced mtDNA-STING activation, hypoxic extracellular-vesicle-mediated mtDNA transfer, macrophage TLR9 signalling, and TFAM-mtDNA-NLRP3 coupling. The transition between immune states remains a testable synthesis, not an established linear pathway. Therapeutic intervention should be matched to signal form, recipient-cell competence, timing, spatial context, and hepatic reserve; pathway activation alone is an inadequate guide.

Chimeric antigen receptor (CAR) T-cell therapy has transformed the treatment of several hematological malignancies, but its broader application remains constrained by the complexity, cost, and time required for conventional ex vivo manufacturing. In vivo CAR T-cell therapy has emerged as a promising next-generation strategy that aims to generate CAR T cells directly within the patient through targeted delivery of CAR-encoding genetic information to endogenous T cells. This approach has the potential to simplify treatment workflows, shorten manufacturing timelines, reduce production costs, and improve the accessibility of CAR-based immunotherapy. In this review, we summarize the conceptual evolution from ex vivo to in vivo CAR T-cell therapy and discuss major delivery platforms for in vivo CAR T-cell generation, including engineered lentiviral vectors (LVs), adeno-associated viral vectors, lipid nanoparticles, polymeric nanoparticles, extracellular vesicles, and fusogenic nanovesicles. We further examine key translational challenges and corresponding optimization strategies, including approaches to improve T-cell targeting specificity and delivery controllability, reduce vector immunogenicity, enhance CAR expression persistence, mitigate safety concerns associated with ectopic transduction or genomic integration, and potentially overcome the physical, antigenic, and immunosuppressive barriers encountered in solid tumors. Finally, we summarize early clinical trial progress and discuss future directions for improving the safety, efficacy, and translational potential of in vivo CAR T-cell therapy. Overall, in vivo CAR T-cell therapy represents an important extension of adoptive cell therapy and may reshape the development and clinical implementation of cell-based immunotherapies.

The optimal choice of chemotherapy regimen for resectable colorectal liver metastases (CRLM) is still undetermined. The study aimed to estimate the impact of perioperative or adjuvant chemotherapy on disease-free survival (DFS), and explore the underlying mechanisms which influence chemotherapy efficacy.

Eight hundred twenty-two patients undergoing curative resection of CRLM were retrospectively collected from May 2018 to December 2023. Treatment effects between perioperative and adjuvant chemotherapy were compared in full subgroup analyses by Kaplan-Meier and Cox proportional hazards methods. Single-cell RNA sequencing and tumor derived organoids were used to explore the molecular mechanisms.

After propensity score matching, 630 patients were enrolled with ratio 1:1 in adjuvant and perioperative chemotherapy group. The median DFS in adjuvant and perioperative group was comparable with 28 and 32.5 months, respectively (HR = 0.99, P = 0.945). Perioperative chemotherapy was associated with improved DFS (25 vs. 13 months, P = 0.039) in patients with a clinical risk score (CRS) of 5. Notably, within the high-risk CRS 4-5 population receiving perioperative chemotherapy, patients with chronic hepatitis B (CHB) had significantly worse DFS (HR = 4.31, 95% CI 1.93-9.64; P < 0.001). Single-cell analyses revealed TSPAN8⁺ stem-like epithelial cells were enriched in sample with CHB. TSPAN8 knockdown sensitized colorectal cancer cells to 5-fluorouracil, and anti-TSPAN8 antibody showed synergistic efficacy with 5-fluorouracil in patient-derived liver metastasis organoids. In addition, the enhanced SPP1-CD44 signaling between TSPAN8⁺ epithelial cells and SPP1⁺ macrophages also contributed to 5-fluorouracil resistance.

Higher CRS identify a subgroup of CRLM patients who may derive greater benefit from perioperative chemotherapy. HBV-related serological profiles is a potential predictor of chemotherapy resistance. The exploratory findings warrants further validation.

Gastrointestinal stromal tumors (GISTs) are rare mesenchymal neoplasms of the gastrointestinal tract. They most often arise in the stomach, followed by the small intestine. Small bowel GISTs usually present with gastrointestinal bleeding, anemia, abdominal pain, or nonspecific symptoms, whereas intestinal obstruction is uncommon because these tumors typically grow outward from the bowel wall. We report the case of a 58-year-old woman with no previous abdominal surgery who presented with one month of abdominal pain, constipation, and vomiting, which progressed to complete absence of stool and flatus for 48 hours. CT and MRI showed a 4.5-cm exophytic distal ileal mass with multiple peritoneal nodules and no liver lesions or lymphadenopathy. Because of the obstructive presentation, exploratory laparoscopy was performed. Intraoperative findings showed a stenosing ileal tumor and diffuse peritoneal implants. Frozen-section analysis of two nodules suggested metastatic GIST, and segmental ileal resection with primary anastomosis was performed to relieve the obstruction and establish a definitive diagnosis. Histology showed a spindle-cell GIST positive for KIT (CD117) and DOG1, with a mitotic rate of 4/50 high-power fields. The peritoneal nodules were metastatic implants. The postoperative course was uneventful, and imatinib 400 mg daily was started one week later. After nearly two years of clinical and radiological follow-up, the patient remained stable without disease progression. This report highlights that ileal GIST should be considered in cases of unexplained small bowel obstruction, especially when imaging shows an exophytic mass without lymphadenopathy.

Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder, often beginning in adolescence and associated with reproductive, metabolic, and psychological complications. The present study evaluated whether adolescent patients meeting the 2023 adolescent-specific PCOS criteria (Rotterdam phenotypes A and B) exhibit poorer mental health or lower quality of life (QoL) in adulthood compared with those with Rotterdam PCOS phenotypes C and D.

A retrospective analysis was conducted among women previously hospitalized in pediatric endocrinology wards and diagnosed with PCOS during adolescence. Clinical data, hormonal profiles, and comorbidities were extracted from medical records. The study group [SG] comprised patients with Rotterdam PCOS phenotypes A and B, while the comparison group [CG] included phenotypes C and D and adolescents at risk of PCOS. In adulthood, participants completed a 66-item survey including self-reported BMI, menstrual symptoms, Ferriman-Gallwey scoring, comorbidity assessment, the Patient Health Questionnaire-9 (PHQ-9), and the WHOQOL-BREF.

A total of 46 individuals completed the survey, including 32 participants in the SG and 14 in the CG. The median age was 22.5 years in the SG and 21.5 years in the CG. All participants were Polish. During adolescence, SG and CG differed in testosterone levels (p = 0.0007) and number of patients with menstrual irregularities (p = 0.006). In adulthood, no significant between-group differences were observed in BMI, Ferriman-Gallwey scores, PHQ-9 outcomes, or WHOQOL-BREF domain scores. The distribution of depressive symptom severity did not differ significantly. Moreover, no correlations were found between QoL or depressive symptoms and BMI change, disease duration or hirsutism. However, mean PHQ-9 scores in both groups indicated clinically relevant depressive symptoms.

Adult women diagnosed with PCOS (Rotterdam phenotypes A and B) in adolescence did not exhibit poorer quality of life or increased depressive symptoms compared with women presenting Rotterdam PCOS phenotypes C and D or adolescents previously classified as being at risk of PCOS. No significant differences were observed between groups in PHQ-9 or WHOQOL-BREF scores, nor were these outcomes related to BMI, hyperandrogenism, or disease duration. Both groups demonstrated elevated depressive symptom levels, highlighting the need for longitudinal studies on long-term psychological outcomes in PCOS.

Acute appendicitis remains a common surgical emergency. The COVID-19 pandemic severely impacted all the health systems globally including surgical emergencies management. This study aimed to assess changes in diagnosis and treatment of acute appendicitis in a tertiary emergency hospital serving an urban population before, during, and after the COVID-19 years.

This was a population-based cohort study including consecutive ≥ 18-year-old residents of a metropolitan area presenting with acute appendicitis at the tertiary emergency hospital. The study period between January 2018 and December 2023 was divided into: 2018-2019 (pre-COVID-19); 2020-2021 (COVID-19); 2022-2023 (post-COVID-19). Comparisons among the three periods were performed using one-way ANOVA and the Chi-square or Fisher's exact test as appropriate.

The breakdown of 1,721 patients included was: 662 in 2018-2019, 422 in 2020-2021, and 637 in 2022-2023. Although the catchment area population (1,817 vs. 1,799 vs. 1,781 MM; p = 0.2), 27 surgeons (27 vs. 27 vs. 27), and 107,202 CT scans (32,048 vs. 38,806 vs. 36,348; p = 0.716) were stable, colonoscopies significantly decreased in 2020-2021 (4,588 vs. 2,457 vs. 4,204; p = 0.012). The number of patients presenting with acute appendicitis decreased during the pandemic, with a relative increase in complicated cases. However, complication and mortality rates did not differ. The postoperative length of stay did not change significantly, despite the increased laparoscopic access rates. The appendiceal neoplasm rates were 2.4% in the COVID-19 and 1.9% in the post-COVID-19 year groups.

This six-year population-based study found a decreased number of patients presenting with acute appendicitis during the pandemic years, with a relative increase in complicated cases but no difference in mortality rates. The rates of appendiceal neoplasms raise concerns regarding the offering of conservative treatment.