Immunotherapy has transformed the therapeutic landscape of advanced cervical cancer, yet clinical benefit remains limited by a highly heterogeneous and immunosuppressive tumor microenvironment. Traditional paradigms, including binary M1/M2 macrophage polarization and models that interpret T-cell dysfunction solely through checkpoint expression, are insufficient to capture the localized intercellular dynamics that drive immune evasion. Recent advances in single-cell and spatial multi-omics have fundamentally reshaped our understanding of this landscape. In this review, we synthesize emerging high-dimensional atlases to reframe macrophage-T-cell crosstalk from simple ligand-receptor interactions into a spatially organized ecological model. We highlight the paradigm shift toward highly resolved myeloid programs, particularly SPP1⁺ and C1QC⁺ macrophage states, and discuss how these programs interact with stromal barriers, regulatory T cells, and metabolic checkpoints to restrict, exclude, or functionally constrain effector T cells within suppressive niches. Crucially, we position persistent high-risk human papillomavirus infection not merely as an initiating carcinogenic trigger, but as an upstream and continuous programmer that rewires innate immune sensing, including context-dependent cGAS-STING-related circuits, to stabilize local immune tolerance throughout disease progression. Finally, we propose translational strategies for distilling complex multi-omic atlases into pathology-compatible prognostic and predictive biomarker signatures. Ultimately, by deciphering these spatially organized networks, this review aims to provide actionable translational insights for targeting macrophage vulnerabilities, guiding biomarker-driven combinatorial immunotherapies, and overcoming immune resistance in cervical cancer.

A subset of cancer patients receiving monoclonal antibody PD-1/PD-L1 inhibitors may develop immune checkpoint inhibitor (ICI)-related neurological complications, such as ICI-related myasthenia gravis(MG)-myositis overlap syndrome and ICI-related myocarditis. Standard management typically involves intravenous immunoglobulin (IVIG), plasma exchange (PE), and high-dose corticosteroids. The use of efgartigimod, a neonatal Fc receptor blocker, for the treatment of ICI-related MG-myositis overlap syndrome remains investigational, with only four relevant cases all representing overlap syndromes (MG with myositis, with or without myocarditis) - reported to date.

This report examines the therapeutic effect of efgartigimod in a patient with cervical cancer who developed ICI-related MG-myositis overlap syndrome after receiving tislelizumab, an anti-PD-1 antibody.

Clinical data from the patient was collected. Relevant laboratory tests and examinations were conducted. Efgartigimod treatment was administered, and clinical severity was evaluated using standardized assessment scales.

A 69-year-old female with cervical cancer developed bilateral ptosis, dysarthria, and limb weakness following tislelizumab therapy. Examination revealed asymmetric ptosis, weak eye closure, and positive fatigability test. Serum creatine kinase was markedly elevated (553.82 U/L); electromyography showed myopathic changes with fibrillation potentials, while repetitive nerve stimulation was negative. Neostigmine test was positive, and anti-acetylcholine receptor antibodies were detected. She was diagnosed with ICI-related MG-myositis overlap syndrome. After four infusions of efgartigimod (10 mg/kg), creatine kinase normalized, the Activities of Daily Living (ADL) score decreased from 10 to 1, and the Quantitative Myasthenia Gravis (QMG) score improved from 16 to 5. The patient was asymptomatic at the 5 months follow-up with no need for a second treatment cycle.

Efgartigimod produced a positive therapeutic effect in this case with ICI-related MG-myositis overlap syndrome. The therapy was well-tolerated, and no adverse events were reported.

Prostate cancer is a common malignancy and major cause of cancer mortality among men worldwide. Early detection improves outcomes, but participation depends on awareness, perceived risk, and attitudes toward testing and diagnostic pathways. In Armenia, many cases are diagnosed at advanced stages, partly due to limited screening practices and low public awareness. This study assessed Armenian men's knowledge of prostate cancer, perception of personal risk, and attitudes toward prostate MRI within early-detection pathways, including perceived barriers to undergoing MRI.

A cross-sectional study was conducted from December 2024 to March 2025 at the Proton Diagnostic and Educational Center in Yerevan, Armenia. The study included 196 men aged ≥45 years undergoing MRI examinations unrelated to prostate conditions. Participants completed a structured 38-item questionnaire adapted from validated international surveys assessing awareness, perceived risk, screening attitudes, and barriers to MRI screening. Four perception scores were derived from Likert-scale responses. Associations between sociodemographic factors and perception scores were examined using multivariable linear regression analysis.

The mean perceived risk score was 2.95 (SD = 0.73) and the mean awareness score was 3.21 (SD = 0.72). Men aged 56-65 years had a 0.30-point higher perceived risk than those aged 45-55 years (mean difference. = 0.30; 95% CI: 0.05-0.55). Awareness was 0.32 points lower among men with secondary education or less (mean difference = -0.32; 95% CI: -0.57 to -0.07). The mean screening confidence score was 3.45 (SD = 0.81). Perceived barriers to MRI screening were higher among men with secondary education or less (mean difference = 0.39; 95% CI: 0.18-0.60) and those with vocational or technical education (adjusted mean difference = 0.40; 95% CI: 0.19-0.61) than among those with higher education.

Awareness of prostate cancer and early detection among Armenian men moderate and varied by education level. Lower educational attainment was consistently associated with lower awareness and greater perceived barriers to MRI-based diagnostic evaluation. Targeted health education and more equitable access to diagnostic services may support earlier detection and help reduce the burden of prostate cancer in Armenia.

To evaluate inflammatory-nutritional indices in relation to breast cancer (BC) risk and mortality and develop a cross-ethnically validated prediction model.

From National Health and Nutrition Examination Survey (NHANES) 2005-2018, 485 BC patients and 16,838 female controls were included, with mortality follow-up through 2019. Weighted multivariate logistic and Cox regression assessed associations between seven inflammatory indices, two composite indicators, and BC risk/mortality. Multiple machine learning (ML) algorithms, including XGBoost, were used to construct risk models. The model was externally validated (NHANES other periods:1999-2004) and cross-ethnic validated. We prospectively enrolled Chinese treatment-naïve breast cancer patients and matched healthy controls for external validation.

In fully adjusted models, the Advanced Lung Cancer Inflammation Index (ALI) was inversely associated with BC risk and all-cause mortality (highest vs. lowest tertile: odds ratio [OR] 0.64, 95% CI 0.45-0.91; hazard ratio [HR] 0.41, 95% CI 0.18-0.90). Conversely, neutrophil percentage-to-albumin ratio (NPAR), systemic inflammation response index (SIRI), and neutrophil-to-lymphocyte ratio (NLR) showed positive associations. ALI outperformed other indices in predicting mortality. XGBoost identified NPAR as the top predictive feature; the model incorporating inflammatory indices and age achieved an AUC of 0.832 on the test set, and a web-based dynamic nomogram incorporating these factors was developed. External validation yielded AUCs of 0.781 (NHANES) and 0.730 (Chinese cohort).

ALI (protective) and NPAR/SIRI/NLR (detrimental) are robust predictors of BC risk and mortality. The ML model demonstrates good predictive performance, but cross-ethnic validation highlights the need for population-specific calibration, which indicated the potential of ML approaches leveraging inflammatory-nutritional indices to enhance BC risk stratification and inform clinical decision-making.

Non-small cell lung cancer (NSCLC) is a leading cause of oncology-related mortality. Although neoadjuvant chemoimmunotherapy (NCIT) improves pathologic response, disease recurrence remains common. Extracapsular extension (ECE) is recognized as a hallmark of aggressive tumor biology across malignancies; however, its prognostic significance in the NCIT setting remains to be fully elucidated. This study aims to evaluate the impact of ECE on survival outcomes in patients with NSCLC following NCIT.

A total of 104 patients with NSCLC and pathologically confirmed lymph node metastasis who underwent surgery following NCIT were retrospectively enrolled. Kaplan-Meier analysis and Cox proportional hazards regression evaluated the prognostic impact of ECE. To minimize selection bias, propensity score matching (PSM) analyses were performed. Time-dependent receiver operating characteristic (ROC) curves assessed predictive accuracy.

ECE-positive patients had significantly worse DFS than ECE-negative counterparts; multivariable analysis confirmed that ECE was an independent prognostic factor for DFS (HR = 2.37, 95% CI: 1.28-4.41, P = 0.006). Furthermore, integrating ECE status with major pathologic response (MPR) substantially improved the predictive accuracy for 2-year DFS compared to MPR alone (AUC increased from 0.591 to 0.706). Although ECE did not significantly affect OS, lymphovascular invasion (LVI) emerged as independent predictor of OS (HR = 3.99, 95% CI: 1.59-10.02, P = 0.003).

ECE remains a potent driver of recurrence following NCIT; intensified postoperative surveillance is warranted for these patients to enable early detection and management of relapse.

Racial disparities in mycosis fungoides (MF) have been described historically, but their persistence in the contemporary era of diagnosis and care remains incompletely characterized. To address this gap, we evaluated survival disparities by race and socioeconomic status (SES) and assessed temporal trends in outcomes. To this end, we used the Surveillance, Epidemiology, and End Results (SEER)-22 database (2000-2021) to identify 13,694 patients with MF. Overall survival (OS) was assessed with Kaplan-Meier analyses and multivariable Cox proportional hazards models. Building on these traditional analyses, we also developed registry-based prognostic models using routinely collected variables with internal validation and geographic/registry-based external validation in a non-overlapping SEER registry subset. Across the study population, the overall 1-, 3-, and 5-year OS rates were 96.8%, 90.8%, and 85.8%, respectively. Survival was lower among Black and American Indian/Alaska Native (AI/AN) patients and highest among Asian/Pacific Islander (API) patients (5-year OS: 85.3% White, 82.7% Black, 92.9% API, 82.1% AI/AN). In multivariable adjusted analyses, Black race remained independently associated with higher mortality, whereas API race was associated with better survival. OS improved modestly in the post-2010 period overall, with a statistically significant improvement among White patients, while changes within other racial groups were not statistically significant. Importantly, lower SES independently predicted worse survival, and Black and AI/AN patients were disproportionately represented in lower-income quartiles; a similar SES distribution pattern was also observed in the National Inpatient Sample. In an integrative Cox model, Black or AI/AN race, older age, male sex, advanced stage, and lower SES independently predicted worse survival. Taken together, these findings indicate persistent racial and socioeconomic inequities in MF survival in the contemporary era. Interpretable prognostic models based on routinely collected variables may therefore support individualized risk stratification and inform efforts to improve equity in MF care.

The management of locally advanced rectal cancer (LARC) has progressively shifted beyond surgery alone toward integrated protocols that include neoadjuvant chemoradiotherapy (nCRT). Even so, the risks of distant metastasis and organ dysfunction remain significant challenges. It is against this backdrop that immune checkpoint inhibitors (ICIs) combined with chemoradiotherapy have begun to redefine therapeutic possibilities. Radiotherapy (RT) induces immunogenic cell death (ICD), enhances antigen presentation, and activates systemic immune responses, whereas ICIs overcome immune suppression by blocking pathways such as PD-1/PD-L1. This synergistic approach converts immunologically cold tumors into infiltrated, hot phenotypes. Building on this rationale, recent Phase II trials have explored immune consolidation following short-course radiotherapy (SCRT) within a total neoadjuvant therapy (TNT) framework. What emerged was particularly compelling: pathological complete response (pCR) rates rose notably, in some cases doubling historical benchmarks. This improvement is not merely a numerical gain; it translates into tangible clinical opportunities, including organ preservation and the feasibility of watch-and-wait (W&W) protocols for selected responders. Notably, SCRT appears especially compatible with subsequent immunotherapy, perhaps due to its abbreviated yet potent immunomodulatory effects, offering a pragmatic alternative to conventional long-course regimens. Looking ahead, the push toward personalization is gaining momentum. Biomarkers like MMR/MSI status, features of the tumor immune microenvironment, and dynamic changes in ctDNA are increasingly guiding trial design and treatment sequencing. While promising, these tools require further validation in larger, more diverse cohorts. Ultimately, the central question remains: how can we convert higher pCR rates into lasting survival benefits while safeguarding quality of life? Answering this will depend on rigorously designed Phase III trials, thoughtful integration of predictive biomarkers, and continued refinement of how and when we combine radiation, chemotherapy, and immunotherapy. Only then can we ensure that advances in biology translate into meaningful human outcomes.

Tissue-resident memory T (TRM) cells provide a conceptual framework for understanding how barrier tissues sense, restrict and amplify immune responses at the earliest sites of danger. Rather than viewing memory primarily through the delayed recruitment of recirculating cells, the TRM perspective places immune memory within defined tissue niches, where cellular position, antigen experience, egress restraint, metabolic adaptation and local cellular interactions collectively determine the quality of in situ surveillance. Here we outline the conceptual evolution and definitional boundaries of TRM cells, distinguish complementary CD4⁺ and CD8⁺ TRM programmes across luminal barriers, and place particular emphasis on TRM cells in tumour surveillance, immunotherapy response, precancerous niches and mammary duct interception. We also integrate recent human reproductive tract phenotyping data to link TRM states with clinically relevant tissue contexts. We argue that future TRM studies should move beyond CD69 or CD103-based annotation and instead build evidence chains that integrate multi-omics, spatial biology, TCR clonality and functional validation. The mammary duct is not a classical mucosal organ, but it may become a critical setting in which to test how far TRM-based principles of in situ immunity can be extended to cancer prevention and local immune intervention.

Immune checkpoint inhibitors (ICIs) can induce a broad spectrum of immune-related adverse events (irAEs), including rare fibroinflammatory autoimmune manifestations. IgG4-related disease (IgG4-RD) has only exceptionally been described following dual ICI therapy.

We report a 65-year-old man with metastatic clear cell renal carcinoma treated with nivolumab plus ipilimumab after nephrectomy. Despite initial radiologic stability, follow-up computed tomography revealed newly developed mass-like lesions in the solitary remaining kidney, raising suspicion of metastatic progression. CT-guided biopsy demonstrated subacute pyelonephritis, acute tubular injury, storiform fibrosis, and dense IgG4-positive plasma cell infiltration consistent with IgG4-RD. Because glucocorticoids were considered potentially detrimental to antitumor immune surveillance, rituximab was selected as steroid-sparing first-line therapy. Two infusions of rituximab (1000 mg each) led to radiologic stabilization/regression of renal lesions while pulmonary metastases remained under oncologic control.

This case highlights IgG4-RD as a rare but clinically important underrecognized irAE of dual ICI therapy that may mimic malignant progression. Histologic confirmation is crucial, and B-cell depletion with rituximab may represent an effective treatment strategy when preservation of antitumor immunity is a priority.

Acute myeloid leukemia (AML) remains a difficult disease to treat, especially in patients with relapsed or refractory disease. While chimeric antigen receptor T cell (CAR-T) therapy has transformed the treatment landscape of several B-cell malignancies, its clinical efficacy in AML has been substantially more limited. This limited efficacy reflects not only challenges in CAR design, but also the complex biological and immunological barriers inherent to AML. Insufficient target specificity, pronounced leukemic heterogeneity, and an immunosuppressive bone marrow microenvironment collectively impair CAR-T cell recognition, persistence, and effector function, thereby restricting both therapeutic efficacy and safety. In this review, we discuss these major barriers and summarize emerging engineering strategies developed to address them, including approaches to improve targeting precision, reinforce CAR-T cell functional fitness, and remodel the suppressive immune niche. Together, these insights may help clarify the key barriers to effective CAR-T therapy in AML and inform future strategies for its optimization.