Christianmeadows8603
Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer with high heterogeneity and dismal survival rates. Tumor immune microenvironment plays a critical role in sensitive to chemotherapy and prognosis. Herein, we determined the relevance of the composition of tumor-infiltrating immune cells to clinical outcomes in PDACs, and we evaluated these effects by molecular subtype.
Data of 1,274 samples from publically available datasets were collected. Molecular subtypes were predicted with support vector machine. Twenty-two subsets of immune cells were estimated with CIBERSORTx. The associations between each cell subset and overall survival (OS), relapse free survival (RFS), and complete response (CR) to chemotherapy were evaluated, modelling cellular proportions as quartiles.
An immune-related cluster was identified with unsupervised hierarchical clustering of hallmark pathways. Of the immune cells investigated, M0 macrophages emerged as closely associated with worse OS (HR =1.23, 95% CI = 1.15-1.31, p=1.57×10
) and RFS (HR = 1.14, 95% CI =1.04-1.25, p=2.93×10
), regardless of molecular subtypes. The CD8+ T cells conferred favorable survival. The neutrophils conferred poor OS overall (HR=1.17, 95% CI=1.10-1.23, p=1.74×10
) and within the classical subtype. In the basal-like subtype, activated mast cells were associated with worse OS. Consensus clustering revealed six immune subgroups with distinct survival patterns and CR rates. The higher expression of PD1 was associated with better OS.
The immune cellular composition infiltrate in PDAC are likely to have effects on prognosis. Further exploration of the cellular immune response has the potential to identify candidates for immunotherapy.
The immune cellular composition infiltrate in PDAC are likely to have effects on prognosis. Further exploration of the cellular immune response has the potential to identify candidates for immunotherapy.Chimeric antigen receptor (CAR) T (CAR-T) cell transfer has made great success in hematological malignancies, but only shown a limited effect on solid tumors. One of the major hurdles is the poor persistence of infused cells derived from ex vivo activation/expansion and repeated antigen encounter after re-infusion. Bcl-xL has been demonstrated to play an important role on normal T cell survival and function as well as genetically engineered cells. In the current study, we developed a retroviral CAR construct containing a second-generation carcinoembryonic antigen (CEA)-targeting CAR with the Bcl-xL gene and tested the anti-CEA CAR-T cell immunotherapy for colorectal cancer. In vitro, the anti-CEA CAR-T cells destroyed CEA-expressing tumor cells and sustained survival. In vivo, adoptive cell transfer of anti-CEA CAR-T cells significantly enhanced the ability of the CAR-T cells to accumulate in tumor tissues, suppress tumor growth and increase the overall survival rate of tumor-bearing mice in a murine model of colorectal cancer. check details These results demonstrate a novel CAR-T platform that has the ability to increase the persistence of CAR-T cells in solid tumors through exogenous expression of persistent genes. The data provide a potentially novel approach to augment CAR-T immunotherapy for solid tumors.
Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) therapy is the routine treatment for patients with metastatic non-small cell lung cancer (NSCLC) harboring positive EGFR mutations. Patients who undergo such treatment have reported cognitive decline during follow-up. This study, therefore, aimed to evaluate brain structural changes in patients receiving EGFR-TKI to increase understanding of this potential symptom.
The medical records of 75 patients with metastatic NSCLC (without brain metastasis or other co-morbidities) who received EGFR-TKI therapy from 2010 to 2017 were reviewed. The modified Scheltens Visual Scale and voxel-based morphometry were used to evaluate changes in white matter lesions (WML) and gray matter volume (GMV), respectively.
The WML scores were higher at the 12-month [8.65 ± 3.86; 95% confidence interval (CI), 1.60-2.35; p < 0.001] and 24-month follow-ups (10.11 ± 3.85; 95% CI, 2.98-3.87; p < 0.001) compared to baseline (6.68 ± 3.64). At the 24-month follopective studies are necessary to confirm our findings.The CXC chemokines belong to a family which includes 17 different CXC members. Accumulating evidence suggests that CXC chemokines regulate tumor cell proliferation, invasion, and metastasis in various types of cancers by influencing the tumor microenvironment. The different expression profiles and specific function of each CXC chemokine in head and neck squamous cell carcinoma (HNSCC) are not yet clarified. In our work, we analyzed the altered expression, interaction network, and clinical data of CXC chemokines in patients with HNSCC by using the following the Oncomine dataset, cBioPortal, Metascape, String analysis, GEPIA, and the Kaplan-Meier plotter. The transcriptional level analysis suggested that the mRNA levels of CXCL1, CXCL2, CXCL3, CXCL5, CXCL6, CXCL8, CXCL9, CXCL10, CXCL11, and CXCL13 increased in HNSCC tissue samples when compared to the control tissue samples. The expression levels of CXCL9, CXCL10, CXCL11, CXCL12, and CXCL14 were associated with various tumor stages in HNSCC. Clinical data analysis showed that high transcription levels of CXCL2, CXCL3, and CXCL12, were linked with low relapse-free survival (RFS) in HNSCC patients. On the other hand, high CXCL14 levels predicted high RFS outcomes in HNSCC patients. Meanwhile, increased gene transcription levels of CXCL9, CXCL10, CXCL13, CXCL14, and CXCL17 were associated with a higher overall survival (OS) advantage in HNSCC patients, while high levels of CXCL1, and CXCL8 were associated with poor OS in all HNSCC patients. This study implied that CXCL1, CXCL2, CXCL3, CXCL8, and CXCL12 could be used as prognosis markers to identify low survival rate subgroups of patients with HNSCC as well as be potential suitable therapeutic targets for HNSCC patients. Additionally, CXCL9, CXCL10, CXCL13, CXCL14, and CXCL17 could be used as functional prognosis biomarkers to identify better survival rate subgroups of patients with HNSCC.
