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.

Immune checkpoint inhibitors (ICIs) activate antitumor immunity by targeting immune checkpoint molecules such as cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), programmed death receptor 1 (PD-1), and programmed death-ligand 1 (PD-L1). They have emerged as a key therapeutic modality for multiple malignancies. Nevertheless, excessive immune activation may trigger a spectrum of immune-related adverse events (irAEs). Though uncommon, uveitis is a sight-threatening irAEs that can result in permanent visual loss. The risk and prognostic outcomes of ICIs-associated uveitis remain poorly defined to date. Therefore, we performed this meta-analysis to systematically assess the correlation of ICIs therapy with uveitis risk and prognosis, with the goal of providing evidence-based recommendations for clinical identification and management of this ocular complication.

We searched PubMed, Embase and Web of Science for cohort studies investigating the association between ICIs therapy and uveitis risk as well as prognosis. The search period was from the database inception to March 2026. The risk of bias of the included studies was assessed with the Risk of Bias in Non-randomized Studies of Interventions (ROBINS-I). The meta-analysis was conducted using RevMan software.

In total, five studies comprising 277,790 participants were finally included. The meta-analysis revealed that ICIs therapy was associated with a significantly higher risk of uveitis (HR = 2.26, 95% CI: 1.46 - 3.51, P = 0.0003). However, no statistically significant association was observed between ICIs-associated uveitis and overall survival in the pooled analysis of two studies (HR = 0.69, 95% CI: 0.35 - 1.39, P = 0.30);this finding is based on limited evidence and should be interpreted with caution.

Current evidence indicates that ICIs therapy was associated with an increased risk of uveitis. However, existing evidence regarding the impact of ICIs-associated uveitis on overall survival is of very low certainty and associated with a high risk of bias, which precludes drawing reliable conclusions. Large-scale prospective multicenter real-world cohort studies are therefore warranted. Such studies should implement standardized ophthalmological assessments and uniform outcome definitions, systematically record anatomical subtypes and severity grades of uveitis, and clarify the relationships between these subtypes/grades and oncologic prognosis as well as systemic immune-related toxicity. Study outcomes should be reported stratified according to cancer type, and further research is required to explore biomarker-based risk prediction.

https://www.crd.york.ac.uk/PROSPERO/view/CRD420261341882, identifier CRD420261341882.

Chimeric antigen receptor (CAR) T-cell therapy has transformed the treatment of relapsed or refractory large B-cell lymphoma, with overall response rates in real-world practice broadly comparable to those in pivotal clinical trials. However, progression-free survival is consistently shorter in real-world cohorts, suggesting that baseline disease characteristics may influence long-term outcomes more than initial treatment sensitivity. This review examines the role of baseline Fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) features as predictors of response and survival after CAR T-cell therapy in lymphoma. We synthesize the evidence on established imaging predictors, including total metabolic tumor volume, extranodal disease distribution and site-specific organ involvement, and bulky disease, and discuss emerging biomarkers such as body composition metrics. Despite a growing body of evidence linking these imaging features to outcomes, clinical adoption has been limited by heterogeneous measurement methodologies, inconsistent definitions, and a lack of prospective validation. We propose practical considerations for structured baseline imaging assessment, including a reporting checklist designed to ensure systematic documentation of the imaging features with demonstrated or emerging prognostic relevance. By moving beyond descriptive staging toward structured, predictive baseline imaging evaluation, radiologists and lymphoma clinicians may improve pretreatment risk stratification and facilitate more informed therapeutic decision-making in the expanding landscape of CAR T-cell therapy.

Bulky tumor (T ≥ 50 mm) significantly compromises treatment outcomes in advanced non-small cell lung cancer (NSCLC) due to excessive tumor burden. Bronchial arterial chemoembolization (BACE) serves as an effective local intervention for reducing tumor size. The combination of immunotherapy and BACE has shown promising efficacy and an acceptable safety profile. However, the effectiveness of this combined regimen in patients with bulky tumors has not been thoroughly investigated.

We conducted a retrospective analysis of 68 patients with advanced NSCLC (IIIB-IVB) who suffered from bulky tumors. Based on first-line treatment, patients were divided into two groups: those who received tislelizumab plus BACE followed by tislelizumab and systemic chemotherapy (Group A, n=34), and those who received tislelizumab plus chemotherapy alone (Group B, n=34). Outcomes included objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety. Prognostic factors for PFS were identified using univariate and multivariate Cox regression analyses.

The ORR was significantly higher in Group A than in Group B (79.41% [27/34] vs 44.12% [15/34], p = 0.006). A significant improvement in median progression-free survival (PFS) was observed in Group A relative to Group B (12.47 months vs 7.73 months, HR: 0.55, 95% CI: 0.30-0.99, p = 0.024). There was no statistically significant difference in median OS between the two groups (20.73 months vs 19.63 months, HR: 0.64, 95% CI: 0.31-1.31, p = 0.071). Multivariate analysis identified the sequential treatment strategy (HR: 2.1, 95% CI:1.13-3.904, p = 0.019) and tumor diameter (HR: 2.263, 95% CI:1.077-4.755, p = 0.031) as independent favorable predictors of PFS. The most frequent grade 3 or higher treatment-related adverse events (TRAEs) included neutropenia (17.65% in group A vs 14.71% in group B), anemia (11.76% vs 17.65%, respectively), and thrombocytopenia (14.71% vs 17.65%, respectively). Regarding BACE-related adverse events, chest pain was reported in one patient (2.94%) in group A, and treatment-related transient cough occurred in four patients (11.76%), all of which were grade 1.

In our cohort of patients with bulky tumors, this sequential strategy was associated with a favorable objective response rate and prolonged median progression-free survival, while maintaining a manageable safety profile.

To investigate the influence of lymph node dissection on the prognosis of unresectable locally advanced gastric cancer (LAGC) after conversion immunochemotherapy (CICT).

A total of 287 patients, including 227 from Nanjing Drum Tower Hospital and an external validation cohort of 60 patients (15 from Peking Union Medical College Hospital, 20 from Beijing Friendship Hospital, and 25 from PLA General Hospital) with pathologically diagnosed unresectable primary LAGC (cT3~4N+) underwent radical gastrectomy after multidisciplinary evaluation conversion immunochemotherapy (CICT) were enrolled, and their clinical data were collected. According to the pathological data of patients' baseline data set, a clinical prediction model of patients' overall survival (OS) and progression-free survival (PFS) was established, and based on COX regression model, the critical value of the number of lymph node dissection was determined by restricted cubic spline (RCS) analysis.

Univariate and multivariate COX regression analysis showed that lymph node metastasis (ypN+) was an independent risk factor for OS (P = 0.030) and PFS (P = 0.002). According to the results of COX regression analysis, the prediction model was established. RCS curve showed that the critical number of lymph node dissection was 21 and 28. Patients with 21-28 lymph node dissection had the best OS and PFS. Compared with the patients with 21-28 lymph nodes dissection, the patients with less than 21 lymph nodes dissection had worse OS (P<0.001) and PFS (P = 0.002). Those with more than 28 lymph nodes isolated had worse OS(P = 0.043) and PFS (P = 0.027). The PFS of patients with more than 28 lymph nodes dissection was better than the patients with less than 21lymph nodes dissection (P = 0.031). Although the difference was not statistically significant, the total OS of patients with more than 28 lymph nodes dissection was still higher than that of patients with less than 21 lymph nodes dissection (P = 0.077).

Among patients after CICT, lymph node metastasis (ypN+) is an independent risk factor for the prognosis of patients. The survival benefit of patients with less than 21 lymph node dissection is significantly reduced, while those with more than 28 lymph node dissection are less than 21-28 lymph node dissection.