-
The EMBO Journal Aug 2023The tumor microenvironment (TME) directly determines patients' outcomes and therapeutic efficiencies. An in-depth understanding of the TME is required to improve the...
The tumor microenvironment (TME) directly determines patients' outcomes and therapeutic efficiencies. An in-depth understanding of the TME is required to improve the prognosis of patients with cervical cancer (CC). This study conducted single-cell RNA and TCR sequencing of six-paired tumors and adjacent normal tissues to map the CC immune landscape. T and NK cells were highly enriched in the tumor area and transitioned from cytotoxic to exhaustion phenotypes. Our analyses suggest that cytotoxic large-clone T cells are critical effectors in the antitumor response. This study also revealed tumor-specific germinal center B cells associated with tertiary lymphoid structures. A high-germinal center B cell proportion in patients with CC is predictive of improved clinical outcomes and is associated with elevated hormonal immune responses. We depicted an immune-excluded stromal landscape and established a joint model of tumor and stromal cells to predict CC patients' prognosis. The study revealed tumor ecosystem subsets linked to antitumor response or prognosis in the TME and provides information for future combinational immunotherapy.
Topics: Humans; Female; Uterine Cervical Neoplasms; Tumor Microenvironment; Ecosystem; Killer Cells, Natural; Immunotherapy
PubMed: 37427448
DOI: 10.15252/embj.2022110757 -
Annals of Palliative Medicine Jan 2024
Topics: Humans; Spinal Neoplasms; Palliative Care; Medical Oncology
PubMed: 38199801
DOI: 10.21037/apm-23-572 -
Neuromodulation : Journal of the... Jul 2023Despite increasing utilization of spinal cord stimulation (SCS), its effects on chemoefficacy, cancer progression, and chemotherapy-induced peripheral neuropathy (CIPN)...
INTRODUCTION
Despite increasing utilization of spinal cord stimulation (SCS), its effects on chemoefficacy, cancer progression, and chemotherapy-induced peripheral neuropathy (CIPN) pain remain unclear. Up to 30% of adults who are cancer survivors may suffer from CIPN, and there are currently no effective preventative treatments.
MATERIALS AND METHODS
Through a combination of bioluminescent imaging, behavioral, biochemical, and immunohistochemical approaches, we investigated the role of SCS and paclitaxel (PTX) on tumor growth and PTX-induced peripheral neuropathy (PIPN) pain development in T-cell-deficient male rats (Crl:NIH-Foxn1) with xenograft human non-small cell lung cancer. We hypothesized that SCS can prevent CIPN pain and enhance chemoefficacy partially by modulating macrophages, fractalkine (CX3CL1), and inflammatory cytokines.
RESULTS
We show that preemptive SCS enhanced the antitumor efficacy of PTX and prevented PIPN pain. Without SCS, rats with and without tumors developed robust PIPN pain-related mechanical hypersensitivity, but only those with tumors developed cold hypersensitivity, suggesting T-cell dependence for different PIPN pain modalities. SCS increased soluble CX3CL1 and macrophages and decreased neuronal and nonneuronal insoluble CX3CL1 expression and inflammation in dorsal root ganglia.
CONCLUSION
Collectively, our findings suggest that preemptive SCS is a promising strategy to increase chemoefficacy and prevent PIPN pain via CX3CL1-macrophage modulation.
Topics: Humans; Rats; Male; Animals; Paclitaxel; Chemokine CX3CL1; Spinal Cord Stimulation; Carcinoma, Non-Small-Cell Lung; Rats, Sprague-Dawley; Lung Neoplasms; Neuralgia; Spinal Cord; Ganglia, Spinal
PubMed: 37045646
DOI: 10.1016/j.neurom.2023.03.006 -
JPMA. the Journal of the Pakistan... Jul 2023Spinal meningiomas are relatively rare, benign, intradural, extramedullary tumours, that are typically slow-growing and well-defined. Surgery is always the first line...
Spinal meningiomas are relatively rare, benign, intradural, extramedullary tumours, that are typically slow-growing and well-defined. Surgery is always the first line for treating spinal meningiomas. Here, we have discussed the existing literature on spinal meningiomas and the role of surgery in determining the outcomes.
Topics: Humans; Meningioma; Spinal Cord Neoplasms; Meningeal Neoplasms
PubMed: 37469082
DOI: 10.47391/JPMA.23-52 -
Brain Pathology (Zurich, Switzerland) Jul 2023H3 K27-altered diffuse midline glioma is a highly lethal pediatric-type tumor without efficacious treatments. Recent findings have highlighted the heterogeneity among...
H3 K27-altered diffuse midline glioma is a highly lethal pediatric-type tumor without efficacious treatments. Recent findings have highlighted the heterogeneity among diffuse midline gliomas with different locations and ages. Compared to tumors located in the brain stem and thalamus, the molecular and clinicopathological features of H3 K27-altered spinal cord glioma are still largely elusive, thus hindering the accurate management of patients. Here we aimed to characterize the clinicopathological and molecular features of H3 K27M-mutant spinal cord glioma in 77 consecutive cases. We found that the H3 K27M-mutant spinal cord glioma, with a median age of 35 years old, had a significantly better prognosis than H3 K27M-mutant brain tumors. We noticed a molecular heterogeneity of H3 K27M-mutant spinal cord astrocytoma via targeted sequencing with 34 cases. TP53 mutation which occurred in 58.8% of cases is mutually exclusive with PPM1D (26%) and NF1 (44%) mutations. The TP53-mutant cases had a significantly higher number of copy number variants (CNV) and a marginally higher proportion of pediatric patients (age at diagnosis <18 years old, p = 0.056). Cox regression and Kaplan-Meier curve analysis showed that the higher number of CNV events (≥3), chromosome (Chr) 9p deletion, Chr 10p deletion, ATRX mutation, CDK6 amplification, and retinoblastoma protein (RB) pathway alteration are associated with worse survival. Cox regression analysis with clinicopathological features showed that glioblastoma histological type and a high Ki-67 index (>10%) are associated with a worse prognosis. Interestingly, the histological type, an independent prognostic factor in multivariate Cox regression, can also stratify molecular features of H3 K27M-mutant spinal cord glioma, including the RB pathway, KRAS/PI3K pathway, and chromosome arms CNV. In conclusion, although all H3 K27M-mutant spinal cord diffuse glioma were diagnosed as WHO Grade 4, the histological type, molecular features representing chromatin instability, and molecular alterations associated with accelerated cell proliferative activity should not be ignored in clinical management.
Topics: Humans; Child; Adult; Adolescent; Histones; Prognosis; Phosphatidylinositol 3-Kinases; Glioma; Brain Neoplasms; Spinal Cord Neoplasms; Mutation; Genomics
PubMed: 36751054
DOI: 10.1111/bpa.13153