Writing 丨 Wang Cong
Edit 丨 Wang Duoyu
WaterwaterPlastic female celloma (GBM) is the most common and fatal brain of adults .Due to the limited treatment plan, the patients ending is miserable, and the median survival period is less than 2 years.Although currently available immunotherapy has proven to benefit various types of cancer patients, including colorectal cancer, melanoma, non -small cell lung cancer, and renal cell carcinoma, but in the clinical trials of GBMs immunotherapy, not proved to be satisfied Effect and ending.
GBM shows significant resistance to the current immunotherapy.Immunoral examination point blocking therapy (ICB) is the main type of current immunotherapy, which aims to enhance the anti -tumor ability of T cells.However, the dense distribution of immunosuppressive cells in GBM tissue and insufficient infiltration of T cells have severely limited ICBs therapeutic potential.In addition, immune escapes are the iconic characteristics of malignant tumors including GBM.GBM can enhance the immunosuppressive effect of tumor microenvironment (TME) through epigenetic modifications such as DNA methylation and promote immune escape.The most severe challenge for GBM immunotherapy is how to overcome highly immunosuppressive gum female cell tumor tumor microenvidic (GBM-TME).
On October 30, 2024, the first affiliated hospital of Sun Yat -sen University Zhang Cross , Liu Xuelong , Zhang Maolei and others published a title: LNC-H19-Derived Protein Shapes The ImmunsoPressive MicroenviBlastoma Research papers.
This study found that -H19 (LNC-H19) encoding an immune-related protein- H19-IRP .The protein played independent of LNC-H19-promote the immunosuppressive suppression of glue maternal cell tumor (GBM) and recruit medullarsia derived cells (MDSC) and tumor-related macrophages (TAM). Cell T cells depletion and immunosuppressive GBM-TME.
H19-IRP is expressed in clinical GBM samples, which can be used as tumor-related antigen (TAA).The research team circulates the LNC-H19 into a ring RNA vaccine- Circh19-VAC , which can trigger a powerful cytotoxic T-cell response for GBM and inhibit GBM growth in the body.This study emphasizes the function of H19-IRP by recruiting MDSC and TAM to generate the function of immunosuppressive GBM-TME, and supports the idea of vaccine used by H19-IRP as the target. Essence
A variety of cell groups of tumor microenvasor (TME), including tumor-related macrophages (TAM), medulular derived inhibitory cells ( MDSC), neutral granulocytes, dendritic cells (DC) and natural killing cells are related to the regulation and promotion of brain tumor progress in immunosuppression.For example, in GBM, macrophages with bone marrow sources tend to show immunosuppressive phenotypes, thereby promoting tumor progress.GBMs single-cell RNA sequencing (SCRNA-SEQ) diagram also shows that the progress of tumor is consistent with the infiltration of immunosupply cells (such as TAM and MDSC).TME with immunosuppressive effects can also affect the curative effect.The infiltration of cytotoxic T cells, memory T cells, TH1 cells, and other lymphocytes in TME often causes poor immunotherapy effects.Based on these discoveries, in recent years, research attempts to transform "cold" TME into "hot" TME as the treatment strategy.However, these strategies are still in the clinical stage and clinical benefits are uncertain.Therefore, it is urgent to find more effective targets to improve or reverse immunosuppressive GBM-TME.
Long -chain non -encoding RNA (LNCRNA) is a non -encoding gene with a length of more than 200NT. It has proven to participate in many physiological and pathological processes, including immunity, including immunity Related functions, such as myelobladia polarization, T cell activation and antigen presentation. LNC-H19 (referred to as H19) is one of the earliest LNCRNA identified and is considered to play the role of cancer genes in a variety of malignant tumors, including glioblastoma (GBM).
H19 plays a role in interacting with MRNA through competitive endogenous RNA (CERNA) mechanism, thereby regulating the expression of genetic genes that are crucial to tumor progress.In addition, H19 can also activate key signal pathways and promote cell survival.These aspects of functions emphasize the complexity of H19s contribution to cancer biology.
It is worth noting that in recent years, the research progress of translation groups has supported some LNCRNAs to actually have the ability to encode functional protein/peptide and enrich the functional spectrum of LNCRNA.For example, the protein encoded in the differential expression of tumors can activate specific T cell responses as tumor -related antigen (TAA) or tumor special antigen (TSA).Due to its important function and expression patterns in tumors, these unveiled LNCRNA encoding proteins may be an important factor in GBM-TME that medium immunosuppressive GBM-TME, and it is expected to become a promising target for GBM.
Cancer vaccine Due to its unique advantages (such as being able to target intracellular and extracellular antigens, stimulate antigen -specific immune responses), it is becoming more and more affected. focus on.Compared with the linear MRNA vaccine, the ring RNA vaccine has a high degree of stability due to its closed ring structure and a long half -life, which is conducive to stable expression.
The ring RNA vaccine has proven to effectively stimulate the immune response of different diseases.Although the circular RNA vaccine has good application prospects, the effective antigen target for GBM still needs to be explored.
In this latest research, the research team found that LNC-H19 can encode protein- H19-IRP .H19-IRP protein (rather than LNC-H19 itself) can promote the infiltration of MDSC/TAM by directly activating the transcription of CCL2 and Galectin-9 by directly activating the transcription of CCL2 and Galectin-9. (GBM-TME) formed a key role in formation.
H19-IRP is highly expressed in GBM cells, so that it can be used as a tumor-related antigen (TAA) to circulate the LNC-H19 to build a ring-shaped RNA vaccine- Circh19-Vac , by expressing H19-IRP, stimulating effective T cell anti-tumor reactions and inhibiting GBM progress in the body.
This study emphasizes H19-IRP by recruiting tumor-related macrophages (TAM) and Impactist cells (MDSC) (MDSC) The function of immunosuppressive gumocyte tumor tumor microenomi environment (GBM-TME) supports the idea of cancer vaccine with H19-IRP as the target for GBM therapy. It also emphasizes LNCRNA The encoded protein is the prospect of the target of tumor immunotherapy.
Thesis link :
https://www.cell.com/cell-- Reports-Medicine/FullText/S2666-3791 (24) 00553-6
