Critical reviews in oncology/hematology最新文献

The tumor immune microenvironment (TIME) comprises a diverse array of cellular and acellular components that collectively influence immune activation and significantly impact treatment outcomes. Among the several immune cell populations within the TIME, myeloid-derived suppressor cells (MDSCs) play a fundamental role in promoting immunosuppression and driving pathological processes, both before and after therapeutic interventions. Pathological conditions such as surgical stress, administration of pharmacological agents, and exposure to anesthetic compounds have been shown to control the accumulation, development, and mobilization of MDSCs, regulatory T cells (Tregs), tumor-associated macrophages (TAMs), and the secretion of pro-inflammatory cytokines by residual tumor cells. These immunological alterations can initiate a network of complex signaling pathways, ultimately contributing to poor prognosis and, notably, tumor relapse. Emerging evidence from recent preclinical studies underscores the importance of the post-treatment pathological state of the TIME in modulating therapeutic efficacy. Therefore, a comprehensive understanding of the post-treatment TIME landscape is essential for the expansion of precise and effective therapeutic strategies intended at preventing tumor recurrence and metastatic relapse. In this review, we explore the intricate molecular mechanisms and interactions that define the post-treatment TIME, with a specific focus on how pathological states influence MDSC expansion and their dual roles in immunosuppression and anti-tumor responses.

Background: Hematopoietic stem cell transplantation (HSCT) is a standard therapy for various hematologic diseases, yet delayed engraftment remains a significant challenge. Mesenchymal stem cells (MSCs) have attracted attention for their potential to enhance hematopoietic recovery due to their immunomodulatory and supportive functions. This systematic review aimed to evaluate the clinical impact of MSC infusion on engraftment outcomes after HSCT.

Method: We systematically searched PubMed, Embase, Scopus, Web of Science, and Cochrane Library for clinical studies published between 2000 and 2025. Eligible studies included randomized trials, cohort studies, and case series that assessed MSCs for improving engraftment. Data were synthesized qualitatively.

Result: Forty-seven studies involving 1777 patients were included. MSCs were primarily derived from bone marrow or umbilical cord and administered intravenously. Approximately 79 % of the studies reported enhanced engraftment, with particular benefit for platelet recovery. The average neutrophil and platelet engraftment times in MSC recipients were 13.96 and 21.61 days, respectively. No serious adverse events related to MSC infusion were reported.

Conclusion: Current clinical evidence supports the safety and potential efficacy of MSCs in promoting hematopoietic engraftment, especially platelet recovery, in HSCT recipients. Further high-quality randomized trials are required to confirm these findings. This systematic review is registered in PROSPERO (CRD420251082387).

Background: Advanced esophageal cell carcinoma (ESCC) is associated with poor survival outcomes. PD-1/PD-L1 inhibitors have been approved for the treatment of advanced ESCC. We aim to study PD-1/PD-L1 inhibitors across other variables in advanced ESCC, including data presented at the September 2024 FDA Oncologic Drugs Advisory Committee (ODAC) meeting.

Methods: On February 28, 2025, we conducted a comprehensive search using PubMed, Web of Science, Scopus, and the Cochrane Library to identify randomized clinical trials evaluating PD-1/PD-L1 inhibitors in advanced ESCC. The primary endpoints were overall survival (OS) and progression-free survival (PFS). Subgroup analyses were performed based on the following variables: age, gender, smoking status, ECOG performance status, liver metastasis, disease stage (locally advanced vs. metastatic), combined positive score (CPS; particularly with cutoff values of CPS 5 and CPS 1-9), and tumor area positivity (TAP). Effect sizes were estimated using the hazard ratio (HR) with random effects model.

Results: Out of 5514 articles screened, only 13 papers were included, involving 6672 patients. PD-1/PD-L1 inhibitors significantly improved OS in both first- and second-line. In the first-line setting (combined with chemotherapy), they reduced the risk of death by 32 % (HR: 0.68; 95 % CI: 0.63-0.74, p < 0.001), while in the second-line setting (used as monotherapy), they reduced mortality by 27 % (HR: 0.73; 95 % CI: 0.66-0.81, p < 0.001). For PFS, a significant benefit was seen only in first-line treatment (HR: 0.62; 95 % CI: 0.58-0.67, p < 0.001) but not in second-line (HR: 0.89; 95 % CI: 0.76-1.04, p = 0.128), with a significant difference between treatment lines (p < 0.001). Most subgroups in our study demonstrated significant survival benefits, except for current smokers (HR: 0.58; 95 % CI: 0.31-1.09; p = 0.089). Finally, all CPS subgroups showed survival benefits in the first-line setting except those with CPS < 1 (PD-L1 negative). A similar pattern was observed in the second-line setting.

Conclusions: PD-1/PD-L1 inhibitors significantly improve OS over chemotherapy in both first- and second-line advanced ESCC. PFS improved only in the first line. More effective therapies for the second line are still needed. Current smokers showed no survival benefit, unlike former or never smokers. OS benefit was absent in PD-L1-negative patients (CPS <1) and greatest in those with CPS ≥ 10.

Lung cancer is one of the leading causes of cancer incidence and mortality. Non-small lung cancer (NSCLC) makes up almost 80 % of lung cancer cases. Treatments for NSCLC have traditionally been restricted to surgeries, radiotherapy, and chemotherapy. However, despite these therapies being able to induce remission in a proportion of patients, many lung cancer patients experience tumor recurrence. To combat high relapse rates, the adoptive transfer of natural killer (NK) cells as NSCLC immunotherapy is attractive as these cells do not require antigen presentation, do not induce GvHD, and can be active in allogeneic settings. However, NSCLC response rates remain low because of the development of resistance mechanisms to NK cell attack. Much of the resistance stems from metabolic reprogramming occurring in the lung cancer tumor microenvironment, owing to aggressive metabolic activity of cancer cells resulting in the production of immunosuppressive metabolites and metabolic byproducts, including oncometabolites. Immune evasion via MHC loss and malignant transformation toward an immunosuppressive niche alters NK cell chemotaxis, reduces their recruitment and impairs their activation. Here, we discuss NSCLC pathophysiology, the immune crosstalk in the NSCLC TME, as well as how the TME, particularly oncometabolite-mediated immunosuppression, metabolic reprogramming and immune dysfunction regulates therapeutic responses and NK cell functional alterations in NSCLC to ultimately drives response resistance.

Background: Immune checkpoint inhibitors (ICIs) have revolutionized gynecologic oncology, but their value in endometrial cancer remains unclear. We conducted this systematic review and meta-analysis to evaluate the efficacy and safety of ICIs in combination with systemic treatment in this setting.

Methods: We searched phase II and III randomized controlled trials comparing systemic therapy with or without ICIs for advanced or recurrent endometrial cancer. We conducted this meta-analysis in two stages, first evaluating any therapy with or without ICIs, then a comparison of chemotherapy alone or with ICIs only. The primary objective of our analysis was to evaluate progression-free survival (PFS) and overall survival (OS). Hazard ratios (HRs) were pooled using random-effects models. Individual patient data were reconstructed from Kaplan-Meier curves for further survival analysis. This meta-analysis is registered in PROSPERO (CRD42025649698).

Results: Six trials with a total of 3826 patients were included in this meta-analysis. In the intention-to-treat population, ICIs improved PFS with HR 0.71 [0.63; 0.81] 95 % confidence interval (95 % CI), p < 0.00001 and OS HR 0.79 [0.68; 0.93], p = 0.004. For dMMR patients, the benefit was pronounced for PFS, HR 0.40 [0.32; 0.49], p < 0.00001 and OS, HR 0.44 [0.33; 0.57], p < 0.00001. For pMMR patients, PFS was improved with HR 0.76, p = 0.002, but no survival benefit with HR at 0.90, p = 0.18.

Conclusion: The addition of ICIs to chemotherapy for advanced or recurrent endometrial cancer significantly improves outcomes, especially for patients with a dMMR profile. For pMMR patients, the gain in PFS was evident, but OS remained immature.

Fatty acids (FA) are essential macromolecules in living organisms and play critical roles in processes such as cancer development, inflammation, and autoimmunity. Immune responses and metabolic changes are involved in tumor occurrence, development, invasion, and metastasis, and therapies targeting immunity and metabolism have gradually begun to be developed in clinical practice. Recent studies have revealed alterations in fatty acid metabolism in tumor microenvironment, suggesting that the modulation of fatty acid metabolism can affect the efficacy of immunotherapy. In this review, we summarize the effects of fatty acids on cancer immunotherapy in aspects including tumor cell metabolism, protein lipid modification, and clinical applications. A deeper understanding of the mechanisms by which FA and their metabolites participate in immune response can enhance our knowledge of their function in tumor development and their impact on the immune system, thereby providing new strategies for improving cancer immunotherapy.

Globally, lung cancer (LC) continues to be the primary cause of cancer-related fatalities. The clinical use of immune checkpoint inhibitors (ICIs) in the treatment of small cell lung cancer (SCLC) follows significantly behind that of non-small cell lung cancer (NSCLC). In advanced NSCLC, combining chemotherapy (CHT) with PD-L1 inhibitors has increased overall survival (OS) and progression-free survival, especially in patients with high PD-L1 expression. Additionally, a new standard of therapy for extensive-stage SCLC has been authorized for atezolizumab in combination with carboplatin and etoposide. However, the combination of PD-L1 inhibitors plus CHT raises the risk of toxicities associated with CHT as well as immune-related side effects such as hepatitis, colitis, and pneumonitis. To minimize side effects, using nanoparticles (NPs) for medication delivery in immunochemotherapy for LC is crucial. In preclinical applications, NPs with transport and/or immunomodulation capabilities have been effectively integrated with ICT. Delivery NPs safeguard and regulate the intended release of their cargo. Generally speaking, we have examined the various ICHT-based LC treatment options in this research. The types of NPs available to mitigate the limitations of this treatment for LC have been studied. Lastly, we covered the clinical constraints and strategies to reduce them. This review article combines evidence from a wide range of sources, including PubMed/NCBI, Google Scholar, and ClinicalTrials.gov, all published within the last few years.

Introduction: Cancer cachexia is a clinical condition characterized by recognizable "sickness behaviors" accompanied by loss of lean body tissue. The Global Leadership on Malnutrition (GLIM) has proposed phenotypic (unintentional weight loss, low body mass index and low muscle mass) and aetiologic (reduced food intake and inflammation or disease burden) diagnostic criteria. Recent work has suggested serum lactate dehydrogenase (LDH) might represent a 3rd aetiologic criteria. Little is known of its relationship with GLIM. A systematic review and meta-analysis of their comparative prognostic value and association was performed.

Methods: A search of electronic databases (PubMed, Medline, Ovid, Cochrane) up to February 2023 was used to identify studies that compared the prognostic value of LDH and components of the GLIM criteria in cancer. An analysis of the relationship between LDH and the components of GLIM was undertaken where this data was available. RevMan 5.4.1 was used to perform a meta-analysis for each diagnostic criteria that had 3 or more studies which reported hazard ratios with a 95 per cent confidence interval for overall survival (OS).

Results: A total of 119 studies were reviewed. Advanced lung cancer was the most studied population. Included in the meta-analysis were 6 studies (n=2165) on LDH and weight loss, 17 studies (n=7540) on LDH and low BMI, 5 studies (n=758) on LDH and low muscle mass, 0 studies on LDH and food intake and 93 studies (n=32,190) on LDH and inflammation. There was a significant association between elevated serum LDH and each of low BMI (OR 1.39, 1.09 - 1.77; p=0.008), elevated NLR (OR 2.04, 1.57 - 2.65; p<0.00001) and elevated CRP (OR 2.58, 1.81 - 3.67; p<0.00001). There was no association between elevated serum LDH and low muscle mass. Only one study presented data on the association between LDH and unintentional weight loss. Elevated LDH showed a comparative OS (HR 1.86, 1.57 - 2.07; p<0.00001) to unintentional weight loss (HR 1.57, 1.23 - 1.99; p=0.0002) and had a similar OS (HR 2.00, 1.70 - 2.34; p<0.00001) to low BMI (HR 1.57, 1.29-2.90; p<0.0001). LDH also showed an OS (HR 2.25, 1.76 - 2.87; p<0.00001) congruous with low muscle mass (HR 1.93, 1.14 - 3.27; p=0.01) and again, LDH conferred as poor an OS (HR 1.77, 1.64-1.90; p<0.00001) as elevated NLR (HR 1.61, 1.48 - 1.77; p<0.00001) or CRP (HR 1.55, 1.43 - 1.69; p<0.00001).

Conclusion: Current literature suggests elevated serum LDH is associated with inflammation in cancer (an aetiologic GLIM criterion), however more work is required to establish the relationship between LDH and the phenotypic components of GLIM. Additionally, elevated serum LDH appears to be a comparative prognosticator of overall survival in cancer when compared to the GLIM criteria.