Adoptive cell therapies have transformed the treatment landscape for hematologic malignancies. Yet, translation to solid tumors remains constrained by antigen heterogeneity, an immunosuppressive tumor microenvironment (TME), and poor persistence of conventional CAR-T cells. In response, innate immune cell platforms, particularly chimeric antigen receptor–engineered natural killer (CAR-NK) cells and chimeric antigen receptor–macrophages (CAR-MΦ), have emerged as promising alternatives. This review summarizes recent advances in the design and application of CAR-NK and CAR-MΦ therapies for solid tumors. We highlight key innovations, including the use of lineage-specific intracellular signaling domains (e.g., DAP12, 2B4, FcRγ), novel effector constructs (e.g., NKG7-overexpressing CARs, TME-responsive CARs), and scalable induced pluripotent stem cell (iPSC)-derived platforms. Preclinical data support enhanced antitumor activity through mechanisms such as major histocompatibility complex (MHC)-unrestricted cytotoxicity, phagocytosis, trogocytosis, cytokine secretion, and cross-talk with adaptive immunity. Early-phase clinical studies (e.g., CT-0508) demonstrate feasibility and TME remodeling with CAR-MΦ. However, persistent challenges remain, including transient in vivo survival, manufacturing complexity, and risks of off-target inflammation. Emerging combinatorial strategies, such as dual-effector regimens (CAR-NK⁺ CAR-MΦ), cytokine-modulated cross-support, and bispecific or logic-gated CARs, may overcome these barriers and provide more durable, tumor-selective responses. Taken together, CAR-NK and CAR-MΦ platforms are poised to expand the reach of engineered cell therapy into the solid tumor domain.

Background: Appendiceal neuroendocrine tumors (NETs) rank as the third most frequent neoplasm affecting the appendix, originating from enterochromaffin cells. This study aims to evaluate the influence of various prognostic factors on the mortality rates of patients diagnosed with NETs of the appendix. Methods: Conducted retrospectively, the study involved 3346 patients, utilizing data sourced from the Surveillance, Epidemiology, and End Results (SEER) database. Our analysis centered on investigating demographic characteristics, clinical features, overall mortality (OM), and cancer-specific mortality (CSM) among the cohort. Variables showing a p-value < 0.1 in the univariate Cox regression were incorporated into the multivariate Cox regression analysis. A Hazard Ratio (HR) > 1 indicated an unfavorable prognosis. Results: In the multivariate analysis, higher OM and CSM were observed in males, older age groups, tumors with distant metastasis, poorly differentiated tumors, and those who underwent chemotherapy. Non-Hispanic Black individuals showed elevated mortality rates. Conclusion: Delayed diagnosis may contribute to the increased mortality in this community. Improved access to healthcare and treatment is crucial for addressing these disparities. Larger prospective studies are needed to pinpoint the underlying causes of elevated mortality in non-Hispanic Black populations, and randomized controlled trials (RCTs) are warranted to evaluate therapies for advanced-stage appendix NETs.

Background: Heart transplantation (Htx) remains the definitive therapy for patients with end-stage heart failure. Despite advancements in mechanical circulatory support (MCS), immunosuppressive strategies, and organ allocation policies, donor availability remains a major limitation. This study analyzes the trends in Htx in the United States between 2016 and 2022, focusing on demographic shifts, mortality trends, and 30-day readmission patterns. Methods: We utilized the National Inpatient Sample (NIS) from 2016 to 2022 and the National Readmissions Database (NRD) for 2021 to identify Htx admissions using ICD-10 PCS code O2YA0Z0. Patient characteristics, mortality rates, and readmission patterns were analyzed using ANOVA and multivariate logistic regression, with statistical significance defined as p < 0.05. Results: The total number of Htx procedures increased from 641 in 2016 to 773 in 2022. The mean age of transplant recipients remained between 45 and 50 years, with no significant differences across years. Racial and socioeconomic disparities persisted, with approximately 60% of transplants occurring in White patients and 21–26% of recipients belonging to the lowest income quartile. All-cause in-hospital mortality remained stable at 4–7%. The 30-day readmission rate in 2021 was 57.7%, with heart failure, transplant rejection, and infections being the leading causes. Peripheral vascular disease (PVD) was the only comorbidity significantly associated with higher 30-day readmission risk (OR: 1.815, 95% CI: 1.477–2.230). Conclusions: Htx utilization has increased over time, driven by improvements in donor allocation and perioperative management. However, racial and socioeconomic disparities remain, and readmission rates continue to be high. Future efforts should focus on optimizing post-transplant care and addressing disparities to improve long-term outcomes.

Background: Intrahepatic cholangiocarcinoma (ICC), a malignancy originating from the epithelial cells of bile ducts, has shown a notable rise in its incidence over the years. It ranks as the second most frequent primary liver cancer after hepatocellular carcinoma. This study investigates how independent prognostic factors, specifically, age and tumor stage, interact to impact mortality in ICC patients. Furthermore, it examines the clinical features, survival rates, and prognostic indicators of ICC cases diagnosed between 2010 and 2017. Methods: Using data from 5083 patients obtained from the Surveillance, Epidemiology, and End Results (SEER) database, this study evaluated demographic and clinical factors alongside overall mortality (OM) and cancer-specific mortality (CSM). Variables achieving a p-value below 0.1 in univariate Cox regression analysis were incorporated into multivariate Cox regression models to identify independent prognostic factors. Hazard ratios (HRs) exceeding 1 were interpreted as markers of poor prognosis. Additionally, this study explored the interaction between age and tumor stage in shaping survival outcomes. Results: The multivariate Cox proportional hazards analysis indicated higher OM in males (HR = 1.19, 95% CI: 1.12–1.26, p < 0.01) and residents of metropolitan counties with populations exceeding 250,000 (HR = 1.15, 95% CI: 1.01–1.31, p < 0.05). Conversely, lower OM was observed in individuals aged 40–59 years (HR = 0.58, 95% CI: 0.38–0.89, p < 0.05), those aged 60–79 years (HR = 0.65, 95% CI: 0.43–0.98, p < 0.05), and patients who received radiation therapy (HR = 0.78, 95% CI: 0.72–0.85, p < 0.01), chemotherapy (HR = 0.54, 95% CI: 0.51–0.58, p < 0.01), or surgery (HR = 0.29, 95% CI: 0.26–0.31, p < 0.01). For CSM, males exhibited higher risks (HR = 1.17, 95% CI: 1.10–1.25, p < 0.01), as did individuals in metropolitan counties with populations over 250,000 (HR = 1.18, 95% CI: 1.03–1.35, p < 0.05). Reduced CSM was observed in patients aged 40–59 years (HR = 0.52, 95% CI: 0.34–0.79, p < 0.01), those aged 60–79 years (HR = 0.57, 95% CI: 0.38–0.86, p < 0.01), and those undergoing radiation therapy (HR = 0.76, 95% CI: 0.70–0.83, p < 0.01), chemotherapy (HR = 0.55, 95% CI: 0.51–0.59, p < 0.01), or surgery (HR = 0.27, 95% CI: 0.25–0.30, p < 0.01). When examining the interaction between age and tumor stage, higher OM was observed in patients aged 40–59 with tumors involving lymph nodes (HR = 1.26, 95% CI: 1.14–2.67, p < 0.05). Similarly, CSM was elevated in patients aged 40–59 with lymph node involvement alone (HR = 2.60, 95% CI: 1.26–5.36, p < 0.05) or with direct spread (HR = 2.81, 95% CI: 1.04–7.61, p < 0.05). Among those aged 60–79, higher CSM was noted in cases with lymph node involvement only (HR = 2.24, 95% CI: 1.11–4.50, p < 0.05) or lymph node involvement accompanied by direct extension (HR = 2.93, 95% CI: 1.10–7.82, p < 0.05). Conclusions: This retrospective analysis, utilizing data from the SEER database, provides new insights into mortality patterns in intrahepatic cholangiocarcinoma (ICC). This study identifies a significant interplay between two key prognostic factors, emphasizing their collective role in influencing mortality outcomes. Despite the predominance of advanced-stage diagnoses, our analysis underscores the substantial survival benefits associated with treatment interventions, with surgical procedures demonstrating the most pronounced impact. These findings highlight the importance of recognizing patients who may benefit from timely and intensive therapeutic strategies. Furthermore, the results underscore the need for future prospective randomized studies to deepen our understanding of these interactions in ICC, particularly as advancements in precision oncology continue to refine patient care.

Background: Esophageal cancer (EC) is the sixth leading cause of cancer-related mortality worldwide, continuing to be a significant public health concern. The purpose of this study is to assess the impact of staging and histopathology of EC on associated mortality. The study also aims to further investigate clinical characteristics, prognostic factors, and survival outcomes in patients diagnosed with EC between 2010 and 2017. Furthermore, we analyzed the interaction between tumor histology and staging and the risk of mortality. Methods: A total of 24,011 patients diagnosed with EC between 2010 and 2017 in the United States were enrolled from the Surveillance, Epidemiology, and End Results (SEER) database. Demographic parameters, tumor stage, and histologic subtypes were analyzed and associated overall mortality (OM) and cancer-specific mortality (CSM) were measured across all subgroups. Covariates reaching the level of statistical significance, demonstrable by a p-value equal to or less than 0.01, were incorporated into a multivariate Cox proportional hazards model. A hazard ratio greater than 1 was indicative of an increased risk of mortality in the presence of the variable under discussion. Additionally, the study explores the interaction between histology and tumor stage on outcomes. Results: The majority of patients were male (80.13%) and non-Hispanic white (77.87%), with a predominant age at diagnosis of between 60 and 79 years (59.86%). Adenocarcinoma was the most common tumor subtype (68.17%), and most patients were diagnosed at a distant stage (41.29%). Multivariate analysis revealed higher mortality risks for males, older patients, unmarried individuals, and those with advanced-stage tumors. Higher income, receiving radiation or chemotherapy, and undergoing surgery were associated with lower mortality. Tumor subtype significantly influenced mortality, with squamous cell carcinoma and neuroendocrine tumors showing higher hazard ratios compared to adenocarcinoma. Adenocarcinoma is linked to a poorer prognosis at advanced stages, whereas the opposite trend is observed for SCC. Conclusions: The study identifies significant demographic and clinicopathologic factors influencing mortality in esophageal cancer patients, highlighting the importance of early diagnosis and treatment intervention. Future research should focus on tailored treatment strategies to improve survival outcomes in high-risk groups and to understand the interaction between tumor histology and tumor stage.