Chinese Journal of Cancer Research最新文献

Objective: The expression of programmed death 1 (PD-1) on CD8⁺ T cells is associated with their activation and exhaustion, while CD57 serves as a senescence marker. The impact of PD-1⁺ and CD57⁺CD8⁺ T cells on the prognosis of patients with advanced high-grade serous ovarian cancer (HGSOC) remain unclear.

Methods: We assessed the percentages of PD-1⁺ and CD57⁺CD8⁺ T cells in tumor-infiltrating lymphocytes (TILs, n=85) and tumor ascites lymphocytes (TALs, n=87) using flow cytometry. The optimal cutoffs for these markers in TILs and TALs were determined through the log-rank maximization method. Gene expression analysis elucidated the tumor immune microenvironment (TIME, n=36).

Results: Patients with higher PD-1⁺CD8⁺ TILs (>87.8%) exhibited longer platinum-free interval (PFI) and overall survival (OS). In contrast, those with elevated CD57⁺CD8⁺ TALs (>28.69%) were more likely to experience chemotherapy and had lower complete remission rates, shorter PFI and OS. PD-1⁺CD8⁺ TILs are primarily displayed an effector memory state with strong proliferative and secretory capabilities. Approximately 50% of CD57⁺CD8⁺ TALs were terminally differentiated, exhibiting significantly impaired proliferation. Based on the proportions of PD-1⁺CD8⁺ TILs and CD57⁺CD8⁺ TALs, patients were categorized into good, median and poor prognosis groups, with median PFI of 47.78, 27.29 and 11.96 months, respectively (P<0.0001). Median OS for these groups was not reach, 49.23 and 30.92 months, respectively (P<0.0001). Patients with poor prognosis exhibit significantly reduced CD8⁺ T cell proportion and increased M2 macrophage in the TIME, alongside downregulation of multiple T cell activation-related pathways.

Conclusions: Lower levels of PD-1⁺CD8⁺ TILs and higher CD57⁺CD8⁺ TALs, assessed prior to treatment, correlated with poor prognosis and suppressive TIME in advanced HGSOC.

[This corrects the article DOI: 10.21147/j.issn.1000-9604.2024.06.11.].

The latest data from the NATALEE trial showed the absolute 3-year invasive disease-free survival benefit was 4.9% between the experimental and control groups. That is to say, in the intermediate-risk hormone receptor positive/human epidermal growth factor receptor-2 negative subgroup, there are also some patients with primary resistance to ribociclib. These patients benefit less from ribociclib, and they are unable to gain significant benefit even with the intensive adjuvant therapy of ribociclib. Considering the drug toxicity and health economic benefits, a 3-year course of ribociclib may not be appropriate for all intermediate-risk populations. Therefore, how to screen out the prime population for intensive adjuvant therapy of ribociclib needs to worth explored. In this paper, we discussed that the adaptive neoadjuvant endocrine therapy can screen out the prime population for intensive adjuvant therapy of ribociclib.

Objective: Recurrence continues to be a pivotal challenge among hormone receptor-positive (HR⁺)/human epidermal growth factor receptor 2-negative (HER2^-) breast cancers. In the international consensus guidelines, HR⁺/HER2^- breast cancer relapse patterns are divided into three distinct types: primary resistant, secondary resistant, and endocrine sensitive. However, owing to the lack of cohorts with treatment and follow-up data, the heterogeneity among different recurrence patterns remains uncharted. Current treatments still lack precision.

Methods: This analysis included data from a large-scale multiomics study of a HR⁺/HER2^- breast cancer cohort (n=314). Through the analysis of transcriptomics (n=312), proteomics (n=124), whole-exome sequencing (n=290), metabolomics (n=217), and digital pathology (n=228) data, we explored distinctive molecular features and identified putative therapeutic targets for patients experiencing recurrence.

Results: We explored distinct clinicopathological characteristics, biological heterogeneity, and potential therapeutic strategies for recurrence. Based on a shared relapse signature, we stratified patients into high- and low-recurrence-risk groups. Patients with different relapse patterns presented unique molecular features in primary tumors. Specifically, receptor tyrosine kinase (RTK) pathway activation in the primary resistant group suggested the utility of RTK inhibitors, whereas mammalian target of rapamycin (mTOR) and cell cycle pathway activation in the secondary resistant group highlighted the potential of mTOR and CDK4/6 inhibitors. Interestingly, the endocrine-sensitive group displayed a quiescent state and high genomic instability, suggesting that targeting quiescent cells and using poly-ADP-ribose polymerase (PARP) inhibitors could be effective strategies.

Conclusions: These findings illuminate the clinicopathological and molecular landscape of HR⁺/HER2^- breast cancer patients with distinct recurrence patterns, highlighting potential targeted therapies.

Objective: The neglect of occult lymph nodes metastasis (OLNM) is one of the pivotal causes of early non-small cell lung cancer (NSCLC) recurrence after local treatments such as stereotactic body radiotherapy (SBRT) or surgery. This study aimed to develop and validate a computed tomography (CT)-based radiomics and deep learning (DL) fusion model for predicting non-invasive OLNM.

Methods: Patients with radiologically node-negative lung adenocarcinoma from two centers were retrospectively analyzed. We developed clinical, radiomics, and radiomics-clinical models using logistic regression. A DL model was established using a three-dimensional squeeze-and-excitation residual network-34 (3D SE-ResNet34) and a fusion model was created by integrating seleted clinical, radiomics features and DL features. Model performance was assessed using the area under the curve (AUC) of the receiver operating characteristic (ROC) curve, calibration curves, and decision curve analysis (DCA). Five predictive models were compared; SHapley Additive exPlanations (SHAP) and Gradient-weighted Class Activation Mapping (Grad-CAM) were employed for visualization and interpretation.

Results: Overall, 358 patients were included: 186 in the training cohort, 48 in the internal validation cohort, and 124 in the external testing cohort. The DL fusion model incorporating 3D SE-Resnet34 achieved the highest AUC of 0.947 in the training dataset, with strong performance in internal and external cohorts (AUCs of 0.903 and 0.907, respectively), outperforming single-modal DL models, clinical models, radiomics models, and radiomics-clinical combined models (DeLong test: P<0.05). DCA confirmed its clinical utility, and calibration curves demonstrated excellent agreement between predicted and observed OLNM probabilities. Features interpretation highlighted the importance of textural characteristics and the surrounding tumor regions in stratifying OLNM risk.

Conclusions: The DL fusion model reliably and accurately predicts OLNM in early-stage lung adenocarcinoma, offering a non-invasive tool to refine staging and guide personalized treatment decisions. These results may aid clinicians in optimizing surgical and radiotherapy strategies.

Objective: Based on the findings of the KEYNOTE-048 study, pembrolizumab in combination with platinum and fluorouracil is the standard first-line treatment for recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC). The efficacy and safety of pembrolizumab combined with nab-paclitaxel and platinum in such patients remain unexplored.

Methods: This single-arm phase 2 study enrolled patients with R/M HNSCC who received pembrolizumab (200 mg), nab-paclitaxel (260 mg/m²), and either cisplatin (75 mg/m²) or carboplatin [area under the curve (AUC) 5] every 21 d for up to six cycles, followed by pembrolizumab maintenance therapy. The primary endpoint was the objective response rate (ORR). Secondary endpoints included disease control rate (DCR), progression-free survival (PFS), duration of response (DoR), overall survival (OS), and safety. Exploratory multi-omics analyses were conducted.

Results: Between April 23, 2021, and August 20, 2023, a total of 67 patients with R/M HNSCC were enrolled and received the study treatment. By the data cut-off date of March 2, 2024, 62 (92.5%) patients had received cisplatin, while five (7.5%) patients had received carboplatin. The median follow-up duration was 12.7 (range: 2.3-34.8) months. The ORR was 62.7%, and the DCR was 88.1%. The median PFS, DoR, and OS were 9.7, 13.0, and 18.7 months, respectively. The most common grade 3 adverse events (AEs) were leukopenia (22.4%) and neutropenia (28.4%). Genomic alterations correlated with efficacy outcomes, and dynamic changes in 17 plasma proteins were associated with treatment response. Upregulation of serum interferon (IFN)-γ and interleukin (IL) 8 levels was linked to treatment-related AEs.

Conclusions: Pembrolizumab in combination with nab-paclitaxel and platinum demonstrated promising efficacy and a manageable safety profile in patients with R/M HNSCC. Future studies are warranted to confirm these findings.

Objective: The laparoscopic approach for locally advanced gastric cancer has recently been adopted based on the results of several randomized controlled trials (RCTs). However, findings from RCTs have not been examined at the national level. This study aimed to investigate the external validity of the Korean Laparoscopic Gastrointestinal Surgery Study-02 (KLASS-02) trial involving 13 tertiary hospitals, using data from the Korean Gastric Cancer Association (KGCA)-led nationwide survey involving 68 tertiary or general hospitals.

Methods: Data on patients who underwent laparoscopic or open distal gastrectomy for pathological stage IB-IIIC gastric cancer under the same conditions were collected from the KLASS-02 trial and the KGCA nationwide survey datasets. Surgical outcomes were assessed for each dataset and multivariable analyses were performed to examine the effect of the laparoscopic approach on surgical outcomes.

Results: The laparoscopic group had a lower overall complication rate than the open group in both KLASS-02 and KGCA datasets (16.1% vs. 23.5% for the KLASS-02 and 12.6% vs. 19.6% for the KGCA). Moreover, the laparoscopic group had fewer wound problems, and fewer grade II, IIIa, and IV complications than the open group in the KGCA data (0.8% vs. 3.4%, 5.8% vs. 10.4%, 2.3% vs. 3.7%, and 0.5% vs. 1.4%, respectively), which were not observed in the KLASS-02 data. Multivariable analyses revealed that the laparoscopic approach was not associated with overall complications, but reduced wound problems and more harvested lymph nodes in the KGCA survey data (adjusted odds ratios, 0.19 for wound problems, adjusted β coefficient 4.39 for number of harvested lymph nodes), which were not shown in the KLASS-02 data.

Conclusions: The safety and feasibility of the laparoscopic approach for locally advanced gastric cancer were validated at a national level. The laparoscopic approach for locally advanced gastric cancer can be implemented in the Republic of Korea.

Exhausted T cell (Tex) is a specific state of T cell dysfunction, in which these T cells gradually lose their effector function and change their phenotype during chronic antigen stimulation. The enrichment of exhausted CD8⁺ T cell (CD8⁺ Tex) in the tumor microenvironment is one of the important reasons leading to the poor efficacy of immunotherapy. Recent studies have reported many reasons leading to the CD8⁺ T cell exhaustion. In addition to cancer cells, myeloid cells can also contribute to T cell exhaustion via many ways. In this review, we discuss the history of the concept of exhaustion, CD8⁺ T cell dysfunction states, the heterogeneity, origin, and characteristics of CD8⁺ Tex. We then focus on the effects of myeloid cells on CD8⁺ Tex, including tumor-associated macrophages (TAMs), dendritic cells (DCs) and neutrophils. Finally, we systematically summarize current strategies and recent advancements in therapies reversing and CD8⁺ T cell exhaustion.

Gastric cancer (GC) ranks 3rd in incidence rate and mortality rate among malignant tumors in China, and the age-standardized five-year net survival rate of patients with GC was 35.9% from 2010 to 2014. The tumor immune microenvironment (TIME), which includes T cells, macrophages, natural killer (NK) cells and B cells, significantly affects tumor progression, immunosuppression and drug resistance in patients with GC. In recent years, immunotherapy has become the first-line or second-line treatment for GC. Lysine-specific demethylase 1 (LSD1, also known as KDM1A) was the first identified human histone demethylase, and high expression of LSD1 in GC is closely related to the dysfunction of the above types of immune cells. Therefore, LSD1 inhibitors could regulate the cytotoxic effects of immune cells against tumor cells through a variety of mechanisms to control tumor progression. In this review, we discuss the effects of LSD1 inhibitors on immune cells in GC and propose LSD1 as a new potential target for immunotherapy in GC.

Objective: Colorectal cancer (CRC) surgeries can be performed using either laparoscopic or open laparotomy approaches. However, the long-term outcomes based on tumor location and age remain unclear. This study compared the long-term outcomes of laparoscopic and laparotomy surgeries in patients with CRC, focusing on tumor location and age to identify suitable subgroups and determine an optimal cut-off age.

Methods: This retrospective study analyzed 2,014 patients with CRC who underwent radical surgery. Patients were categorized into laparoscopy and laparotomy groups, and propensity score matching (PSM) was performed. Kaplan-Meier analysis, log-rank tests, and Cox regression models were used to identify the independent factors affecting overall survival (OS).

Results: Analysis results before PSM indicated higher OS in the laparoscopy group (P=0.035); however, it was no significant difference in mean OS between the two groups after PSM analysis. Cox regression analysis identified several factors influencing the OS of patients with CRC, with age, T stage, nodal involvement, poorly differentiated adenocarcinoma, ascites, preoperative intestinal obstruction, and local tumor spread as independent risk factors. Family history was a protective factor [hazard ratio (HR)=0.33; 95% CI, 0.16-0.68; P=0.002], and the surgical modality did not independently affect OS. The subgroup analysis highlighted the advantages of laparoscopic surgery in specific subgroups.

Conclusions: Overall, laparoscopic and laparotomy surgeries resulted in similar mid- and long-term prognoses for patients with CRC. Laparoscopic surgery showed better outcomes in specific subgroups, particularly in patients aged >60 years and in those with right-sided colon carcinoma. This study suggests that age >64 years might be the optimal cut-off age for laparoscopic surgery.