About this Research Topic
Lysosomes are membrane-bound vesicles that contain two types of proteins necessary for maintaining their structure and function: soluble lysosomal hydrolases and lysosomal membrane proteins. The former performs digestive functions, while the latter has more complex functions such as proton pumping and promoting intercellular interactions. Lysosomes are not only the endpoint of multiple transport pathways (including autophagy, endocytosis, and phagocytosis), but also a platform for recruiting and activating mTOR, which regulates cell metabolism, growth, and differentiation. The central position of lysosomes in communication and convergence of multiple pathways determines their critical and irreplaceable roles in cell metabolism, proliferation, differentiation, immunity, and death. Cancer cells can upregulate metabolism to meet their growth and proliferation needs by altering the quantity, location, and activity of lysosomes.
Changes and dysfunction of lysosomes also play an important role in cancer cells' escape from the host immune system. Lysosomal degradation is not only responsible for antigen processing but also controls the presentation of MHC-I on the cell membrane. It has been reported that MHC-I expression on the cell surface of pancreatic ductal adenocarcinoma (PDAC) cells is reduced due to autophagy-dependent lysosomal degradation of MHC-I. MHC-I was found to coexist with autophagosomes and lysosomes in PDAC cells, and inhibition of autophagy restored MHC-I levels and promoted T cell response in mouse models. In addition, the loss or blockade of tumor cell co-stimulatory molecules is one of the important mechanisms of tumor immune escape. Lysosomes are responsible not only for the degradation of immune checkpoints such as CTLA-4, PD-L1, and CD47 but also for the membrane transport and presentation of these immune checkpoints. CMTM6 co-localizes with PD-L1 on the cell membrane and intracellular vesicles, inhibiting lysosomal degradation of PD-L1. PD-L1 interacts with PD-1 on T cells to evade T cell-mediated immune protection. Therefore, developing strategies for targeting lysosomes in cancer immunotherapy is feasible and may provide us with a window of opportunity for treatment.
Among our research topics, original research and review articles are welcome, but not limited to the following topics:
(1) Study the mechanisms of lysosomes in tumor immunotherapy, including the interaction between lysosomes and tumor cells, and the regulatory effect of lysosomes on immune cells.
(2) Perform multi-omics analysis to explore differentially expressed genes, and further analyze their functions and pathways, in order to investigate the mechanism of tumor formation and transcriptional regulatory network, and provide new targets and targeting strategies for lysosome-targeted tumor immunotherapy.
(3) Design and develop targeted drugs: design lysosome-targeted drugs with high selectivity and affinity for different types of tumors, and explore new targeting strategies such as targeting novel antigens on the surface of tumor cells and targeting novel receptors on tumor cells.
(4) Data mining and artificial intelligence: use machine learning, deep learning, and other methods to mine and analyze large-scale bioinformatics data, discover potential biomarkers, biological pathways, and targeting strategies, and provide new insights and methods for lysosome-targeted tumor immunotherapy.
Manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by robust and relevant validation (clinical cohort or biological validation in vitro or in vivo) are out of scope for this topic.
Changes and dysfunction of lysosomes also play an important role in cancer cells' escape from the host immune system. Lysosomal degradation is not only responsible for antigen processing but also controls the presentation of MHC-I on the cell membrane. It has been reported that MHC-I expression on the cell surface of pancreatic ductal adenocarcinoma (PDAC) cells is reduced due to autophagy-dependent lysosomal degradation of MHC-I. MHC-I was found to coexist with autophagosomes and lysosomes in PDAC cells, and inhibition of autophagy restored MHC-I levels and promoted T cell response in mouse models. In addition, the loss or blockade of tumor cell co-stimulatory molecules is one of the important mechanisms of tumor immune escape. Lysosomes are responsible not only for the degradation of immune checkpoints such as CTLA-4, PD-L1, and CD47 but also for the membrane transport and presentation of these immune checkpoints. CMTM6 co-localizes with PD-L1 on the cell membrane and intracellular vesicles, inhibiting lysosomal degradation of PD-L1. PD-L1 interacts with PD-1 on T cells to evade T cell-mediated immune protection. Therefore, developing strategies for targeting lysosomes in cancer immunotherapy is feasible and may provide us with a window of opportunity for treatment.
Among our research topics, original research and review articles are welcome, but not limited to the following topics:
(1) Study the mechanisms of lysosomes in tumor immunotherapy, including the interaction between lysosomes and tumor cells, and the regulatory effect of lysosomes on immune cells.
(2) Perform multi-omics analysis to explore differentially expressed genes, and further analyze their functions and pathways, in order to investigate the mechanism of tumor formation and transcriptional regulatory network, and provide new targets and targeting strategies for lysosome-targeted tumor immunotherapy.
(3) Design and develop targeted drugs: design lysosome-targeted drugs with high selectivity and affinity for different types of tumors, and explore new targeting strategies such as targeting novel antigens on the surface of tumor cells and targeting novel receptors on tumor cells.
(4) Data mining and artificial intelligence: use machine learning, deep learning, and other methods to mine and analyze large-scale bioinformatics data, discover potential biomarkers, biological pathways, and targeting strategies, and provide new insights and methods for lysosome-targeted tumor immunotherapy.
Manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by robust and relevant validation (clinical cohort or biological validation in vitro or in vivo) are out of scope for this topic.
Keywords: Lysosomes，cell metabolism，immunotherapy，multi-omics analysis, targeted drugs
Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.
