Enhancing Anti-Cancer Immune Response by Acidosis-Sensitive Nanobody Display.

One of the main challenges with many cancer immunotherapies is that biomarkers are needed for targeting. These biomarkers are often associated with tumors but are not specific to a particular tumor and can lead to damage in healthy tissues, resistance to treatment, or the need for customization for different types of cancer due to variations in targets. A promising alternative approach is to target the acidic microenvironment found in most solid tumor types. This can be achieved using the pH (Low) Insertion Peptide (pHLIP), which inserts selectively into cell membranes under acidic conditions, sparing healthy tissues. pHLIP has shown potential for imaging, drug delivery, and surface display. For instance, we previously used pHLIP to display epitopes on the surfaces of cancer cells, enabling antibody-mediated immune cell recruitment and selective killing of cancer cells. In this study, we further explored this concept by directly fusing an anti-CD16 nanobody, which activates natural killer (NK) cells, to pHLIP, eliminating the need for antibody recruitment. Our results demonstrated the insertion of pH-sensitive agents into cancer cells, activation of the CD16 receptor on effector cells, and successful targeting and destruction of cancer cells by high-affinity CD16+ NK cells in two cancer cell lines.

被引量：- 发表：1970

Evolution of Bioelectric Membrane Potentials: Implications in Cancer Pathogenesis and Therapeutic Strategies.

Electrophysiology typically deals with the electrical properties of excitable cells like neurons and muscles. However, all other cells (non-excitable) also possess bioelectric membrane potentials for intracellular and extracellular communications. These membrane potentials are generated by different ions present in fluids available in and outside the cell, playing a vital role in communication and coordination between the cell and its organelles. Bioelectric membrane potential variations disturb cellular ionic homeostasis and are characteristic of many diseases, including cancers. A rapidly increasing interest has emerged in sorting out the electrophysiology of cancer cells. Compared to healthy cells, the distinct electrical properties exhibited by cancer cells offer a unique way of understanding cancer development, migration, and progression. Decoding the altered bioelectric signals influenced by fluctuating electric fields benefits understanding cancer more closely. While cancer research has predominantly focussed on genetic and molecular traits, the delicate area of electrophysiological characteristics has increasingly gained prominence. This review explores the historical exploration of electrophysiology in the context of cancer cells, shedding light on how alterations in bioelectric membrane potentials, mediated by ion channels and gap junctions, contribute to the pathophysiology of cancer.

被引量：- 发表：1970

Beyond Hormones: Investigating the Impact of Progesterone Receptor Membrane Component 1 in Lung Adenocarcinoma.

Progesterone Receptor Membrane Component 1 (PGRMC1) is a candidate oncogene with a prominent involvement in the pathogenesis of diverse cancers (ovarian, thyroid, breast, colon, head, and neck). Our study ascertains the ability of PGRMC1 to influence WNT members in the non-small cell lung cancer subtype-lung adenocarcinoma (LUAD) and participates in augmented cell proliferation and migration. Both computational and in vitro experimental analyses were performed in this study. Gene silencing, in vitro assays, gene expression & and protein expression studies were performed to ascertain the role of PGRMC1 in LUAD cells. The computational analysis, PGRMC1 gene level expression was analysed using the microarray gene expression omnibus datasets (GSE27262; GSE18842) to compare LUAD tumours and normal tissues. Concurrently, the gene expression profiling interactive analysis of PGRMC1 and Kaplan-Meier survival analysis revealed a decreasing patient survival rate with an increasing PGRMC1 gene expression in LUAD tumour samples. Interestingly, the experimental gene silencing studies were conducted in vitro (si-PGRMC1 Vs si-Control) to understand the essential role of PGRMC1 in regulating WNT-associated genes (WNT1, WNT5A, and WNT11). Comparative experimental cell migration and spheroid formation assays (si-PGRMC1 Vs si-Control) in vitro showed a strong association between PGRMC1 and LUAD. In vitro expression analysis using real-time PCR and western blot further confirmed the connecting link between PGRMC1 and WNT5A compared to other WNT member genes (WNT1 and WNT11) in LUAD. The computational and experimental analyses agreed with one another.

被引量：- 发表：1970

Editorial.

被引量：- 发表：2024

Construction and Analysis of a Mitochondrial Metabolism-Related Prognostic Model for Breast Cancer to Evaluate Survival and Immunotherapy.

As one of the most prevalent malignancies among women, breast cancer (BC) is tightly linked to metabolic dysfunction. However, the correlation between mitochondrial metabolism-related genes (MMRGs) and BC remains unclear. The training and validation datasets for BC were obtained from The Cancer Genome Atlas and Gene Expression Omnibus databases, respectively. MMRG-related data were obtained from the Molecular Signatures Database. A risk score prognostic model incorporating MMRGs was established based on univariate, LASSO, and multivariate Cox regression analyses. Independent factors affecting BC prognosis were identified through regression analysis and presented in a nomogram. Single-sample gene set enrichment analysis was employed to assess the immune levels of high-risk (HR) and low-risk (LR) groups. The sensitivity of BC patients in the two groups to common anti-tumor drugs was evaluated by utilizing the Genomics of Drug Sensitivity in Cancer database. 12 MMRGs significantly associated with survival were selected from 1234 MMRGs. A 12-gene risk score prognostic model was built. In the multivariate regression analysis incorporating classical clinical factors, the MMRG-related risk score remained an independent prognostic factor. As revealed by tumor immune microenvironment analysis, the LR group with higher survival rates had elevated immune levels. The drug sensitivity results unmasked that the LR group demonstrated higher sensitivity to Irinotecan, Nilotinib, and Oxaliplatin, while the HR group demonstrated higher sensitivity to Lapatinib. The development of MMRG characteristics provides a comprehensive understanding of mitochondrial metabolism in BC, aiding in the prediction of prognosis and tumor microenvironment, and offering promising therapeutic choices for BC patients with different MMRG risk scores.

被引量：- 发表：1970