Objective This study aims to investigate the perioperative experience and needs of patients with liver cancer for interventional therapy, in order to provide the basis for further improving a patient’s medical experience and satisfaction. Methods A semi-structured in-depth interview was conducted for 16 patients with liver cancer in interventional therapy using the phenomenological research method of qualitative research. The themes were analyzed, summarized, refined and extracted using the Colaizzi analytical procedure. Results The study results revealed that the perioperative experience and needs of patients with liver cancer for interventional therapy could mainly be summarized into seven themes: anxiety, fear and helplessness; not understanding the specific procedures of interventional therapy; worrying that the disease would not be treated as expected; lack of understanding of perioperative adverse reactions and the inability to cope with these; concern on the financial burden of health care costs on families; concerned on the physical and mental health of the dependent; the further improvement of diagnosis and treatment procedures. Conclusion Patients with liver cancer undergo a complex psychological experience during interventional therapy. In clinical practice, a patient’s psychological needs and changes should be valued, in order to provide a targeted psychological intervention, health guidance and social support, thereby improving the medical experience and satisfaction of patients.
Objective: To observe the relationship between the expression of PETA-3 and clinicopathological factors in breast cancer. Methods: 40 breast cancer samples were detected by the real-time PCR and immunohistochemical staining to analyze the expression of PETA-3. The relationship between the expression of and clinicopathological factors was analyzed. Results: Compared to that in the adjacent tissues, the expression of PETA-3mRNA was markedly increased in breast cancer tissues. PETA-3 expression was significantly higher in metastatic breast cancer than in non-metastatic tumors. Furthermore PETA-3 expression levels of breast cancer were correlated with estrogen receptor status. Conclusions: Increased expression of PETA-3 suggests its involvement in the pathogenesis and metastasis of breast cancer.
Papillary renal cell carcinoma (PRCC) is one of the most common histological subtypes of renal cell carcinoma. Type 1 and type 2 PRCC are reported to be clinically and biologically distinct. However, little is known about immune infiltration and the expression patterns of immune-related genes in these two histologic subtypes, thereby limiting the development of immunotherapy for PRCC. Thus, we analyzed the expression of 22 immune cells in type 1 and type 2 PRCC tissues by combining The Cancer Genome Atlas (TCGA) database with the ESTIMATE and CIBERSORT algorithms. Subsequently, we extracted a list of differentially expressed genes associated with the immune microenvironment. Multichip mRNA microarray data sets for PRCC were downloaded from the Gene Expression Omnibus (GEO) to further validate our findings. We found that the immune scores and stromal scores were associated with overall survival in patients with type 2 PRCC rather than type 1 PRCC. Tumor-infiltrating M1 and M2 macrophages could predict the clinical outcome by reflecting the host’s immune capacity against type 2 PRCC. Furthermore, CCL19/CCR7, CXCL12/CXCR4, and CCL20/CCR6 were shown to be potential new targets for tumor gene therapy in type 2 PRCC. Our findings provide valuable resources for improving immunotherapy for PRCC.
Abstract Background: Antibody Drug Conjugates (ADCs) targeting Trophoblast Cell-Surface Antigen 2 (TROP2) are emerging as paradigm-changing drugs, but the therapeutically relevant mechanisms of TROP2 itself remain unknown. The goal of this project is to investigate the role of TROP2 in promoting breast cancer aggressiveness and provide insights into the mechanisms of action of TROP2-targeted ADCs. Methods: TROP2 loss-of-function studies were performed in multiple syngeneic mouse mammary tumor models. Truncated TROP2 mutants were reconstituted into CRISPR knockout cells to map essential domains that enable TROP2 tumor-promoting activity. Flow cytometry for tumor infiltrating lymphocytes, tissue histology and immunofluorescence were used to assess tumor microenvironment. Data from immune checkpoint-treated patients were used to test hypotheses from the preclinical findings. Results: We find that TROP2 mediates a mechanism of immune exclusion in Triple-Negative Breast Cancer (TNBC) through association with the essential tight junction protein Claudin 7. TROP2 expression is inversely correlated with T cell infiltration and strongly associated with outcomes in TNBC. Loss-of-function and reconstitution experiments demonstrate TROP2 is sufficient to drive tumor progression in vivo in a CD8 T cell-dependent manner, while its loss deregulates expression and localization of multiple claudins, enabling T cell infiltration. Employing a humanized TROP2 syngeneic TNBC model, we show that TROP2 targeting via Sacituzumab govitecan (SG) induces an anti-PD1 response associated with broad immune cell activation, and TROP2 is highly associated with lack of response to anti-PD1 therapy in human breast cancer. Conclusions: TROP2 mediates immune exclusion and may be targeted to enhance immunotherapy response. Citation Format: Bogang Wu, Win Thant, Elena Bitman, Ting Liu, Jie Liu, Eleftherios I. Paschalis, Katherine H. Xu, Linda T. Nieman, David T. Ting, Nayana Thimmiah, Sheng Sun, Rachel O. Abelman, Steven J. Isakoff, Laura M. Spring, Aditya Bardia, Leif W. Ellisen. A TROP2/Claudin program mediates immune exclusion to impede checkpoint blockade in breast cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor Immunology and Immunotherapy; 2024 Oct 18-21; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2024;12(10 Suppl):Abstract nr PR-04.
Abstract Purpose Targeted therapy has not been effective for small cell lung cancer (SCLC) patients. Although some studies have reported on EGFR mutations in SCLC, a systematic investigation into the clinical, immunohistochemical, and molecular characteristics and prognosis of EGFR-mutated SCLCs is lacking. Methods Fifty-seven SCLC patients underwent next-generation sequencing technology, with 11 in having EGFR mutations (group A) and 46 without (group B). Immunohistochemistry markers were assessed, and the clinical features and first-line treatment outcomes of both groups were analyzed. Results Group A consisted primarily of non-smokers (63.6%), females (54.5%), and peripheral-type tumors (54.5%), while group B mainly comprised heavy smokers (71.7%), males (84.8%), and central-type tumors (67.4%). Both groups showed similar immunohistochemistry results and had RB1 and TP53 mutations. When treated with tyrosine kinase inhibitors (TKIs) plus chemotherapy, group A had a higher treatment response rate with overall response and disease control rates of 80% and 100%, respectively, compared to 57.1% and 100% in group B. Group A also had a significantly longer median progression-free survival (8.20 months, 95% CI 6.91–9.49 months) than group B (2.97 months, 95% CI 2.79–3.15), with a significant difference ( P = 0.043). Additionally, the median overall survival was significantly longer in group A (16.70 months, 95% CI 1.20–32.21) than in group B (7.37 months, 95% CI 3.85–10.89) ( P = 0.016). Conclusion EGFR-mutated SCLCs occurred more frequently in non-smoking females and were linked to prolonged survival, implying a positive prognostic impact. These SCLCs shared immunohistochemical similarities with conventional SCLCs, and both types had prevalent RB1 and TP53 mutations.
Objective This study evaluates the cost-effectiveness of tislelizumab plus chemotherapy as a first-line treatment for locally advanced or metastatic (IIIB/IV) nonsquamous non-small cell lung cancer (nsq-NSCLC) in China.
Abstract Antibody Drug Conjugates (ADCs) are proving to be groundbreaking therapeutics for all breast cancer subtypes. Sacituzumab govitecan (SG), an ADC targeting the TROP2 tumor antigen and harboring a topoisomerase 1 inhibitor payload, improves overall survival in advanced Hormone Receptor positive (HR+) and Triple Negative Breast Cancer (TNBC). However, SG has not been tested in early-stage breast cancer, and response predictors and mechanisms of resistance to SG in any setting remain to be defined. We thus designed the NeoSTAR trial, a Phase 2 study of response-guided neoadjuvant SG for localized TNBC, in which 50 patients received single-agent SG followed by imaging and tumor bed biopsy, with subsequent therapy determined by clinical and pathologic response. We collected fresh pre-treatment and post-SG biopsies and carried out analysis employing single-cell RNAseq, exome sequencing, and spatial analysis. As anticipated, cell composition of TNBCs between subjects was highly heterogenous but revealed non-tumor cell types predictive of pathologic complete response (pCR) to SG alone. As in the metastatic setting, tumor cell TROP2 levels were variable both within and between TNBCs, and were not predictive of response to SG. In contrast, we identified tumor cell-intrinsic pathways predictive of response that were the same as those identified in parallel genome-wide CRISPR screens for SG response pathways in TNBC. Analysis of matched pre/post treatment specimens demonstrated substantial clonal selection and clonal evolution post SG. Of particular interest were small subpopulations of tumor cells with shared properties that were present in multiple tumors in very small numbers pre-treatment but dramatically expanded post-treatment, suggesting the presence of a common resistance phenotype. Ongoing work to be presented focuses on defining the nature of the shared resistant subpopulations, and on comprehensively assessing the genomic correlates of response to SG versus standard chemotherapy. In summary, detailed single-cell and genomic analysis of single-agent ADC therapy in treatment-naïve primary TNBC reveals how intratumoral heterogeneity and subclonal resistance phenotypes shape the landscape of treatment response. These observations provide new insights relevant to the clinical application of this complex class of therapeutics. Citation Format: Laura M. Spring, Bogang Wu, Ting Liu, Jacob Geisberg, Simona Cristea, Veerle Bossuyt, Rachel Occhiogrosso Abelman, Nicole Peiris, James Coates, Siang-Boon Koh, Mengran Zhang, Lianne Ryan, Beverly Moy, Steven J. Isakoff, Sara M. Tolaney, Franziska Michor, Aditya Bardia, Leif W. Ellisen. Intratumoral heterogeneity drives resistance to Antibody Drug Conjugate therapy: Analysis of the NeoSTAR trial of neoadjuvant Sacituzumab govitecan for localized TNBC [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Breast Cancer Research; 2023 Oct 19-22; San Diego, California. Philadelphia (PA): AACR; Cancer Res 2024;84(3 Suppl_1):Abstract nr PR08.
Abstract Background : Abundant evidence suggests that tumor immune infiltration was involved in the occurrence of ovarian cancer (OvCa). Current studies have demonstrated the effect of tumor-infiltrating immune cells (TIICs) on OvCa development; few studies have found the immune genomic profile and immune subclasses of OvCa based on transcriptome data, which may help to optimally stratify patients who respond to immunotherapy. Methods : Based on the two publicly available OvCa transcriptomics data, three immunogenomic subgroups were classified using unsupervised hierarchical clustering. The GO and KEGG were analyzed in each subtype. Response to immunotherapy and anti-cancer drug targets was predicted by the TIDE, Submap algorithm, and GDSC dataset. Results : The three types of immunogenomic OvCa subsets were classified based on immune signatures. We identified three OvCa subtypes, termed hyperimmunogenic (Immunity_H), moderately immunogenic (Immunity_M), and hypoimmunogenic (Immunity_L). Each subtype has specific pathways. In the Immunity_H subtype, a number of cancer-related and immune-related pathways are overactivated. In contrast, the Immunity_L subtype is predominantly enriched in lipid metabolism. Immunity_H subtype has higher immune cell infiltration, antitumor immunoreactivity, and better survival prognosis compared to other subtypes. Predicted clinical response to immune checkpoint blockade was used by Submap and TIDE algorithm and screened potential chemotherapeutic drug targets for OvCa was employed using GDSC. After the prediction for potential drug targets, we identified several potential drug targets for the treatment of OvCa, including Parthenolide and AKT inhibitor VIII, Paclitaxel. Also,Immunity_H subgroup has an early FIGO stage, and was susceptible to respond to immunotherapy. Conclusions : The characterization of immune-based OvCa subgroups possessed potential clinical implications for OvCa treatment and has the potential to guide personalized treatment of OvCa patients through immunotherapy.
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