Microorganisms, self-destruction and the immune system

4 min read


Debiopharm commences pivotal glioblastoma therapy study Debiopharm has announced the beginning of its open-label phase 1/2 research study into Debio 0123.  Debio 0123 is to be used in combination with temozolomide (TMZ) in patients with recurrent or progressive glioblastoma (GBM). Preclinical data has demonstrated that the drug is able to enter the brain and successfully slow tumour growth. In addition, the combination of Debio 0123 with TMZ has been shown to significantly increase antitumour activity. The study will also investigate the combination of Debio 0123 with TMZ/Radiotherapy (standard of care) in newly diagnosed patients.  


Phenotypic diversity of T cells in human primary and metastatic brain tumours revealed by multiomic interrogation In a healthy brain, the immune system is tightly controlled to prevent neuroinflammation. However, after cancer development, there is a conflict between keeping the immune system tightly controlled and activating the immune system against the tumour. To work out the potential roles of T cells (immune cells) in this process, the study, published in Nature Cancer, investigated T cells in individuals with primary or metastatic brain cancers. Their analysis revealed that a subgroup of individuals with brain metastasis had a high proportion of potentially tumour-reactive T (pTRT) cells. The study goes on to conclude that in certain brain metastases the immune system may react to the tumour via the T cells, and that analysis of the tumour may inform who could benefit from immunotherapy. 

Microbial peptides activate tumour-infiltrating lymphocytes in glioblastoma Published in Nature, this study followed several experimental paths to investigate microorganisms and their potential role in immune reactivity against glioblastoma.  Along with other learnings, the researchers demonstrated that both glioblastoma tissue and tumour cell lines present bacteria-specific peptides (chemicals) on their cell surface. Researchers then went on to determine whether tumour-infiltrating white blood cells (lymphocytes) recognised these bacterial peptides that came from the tumour. They showed that peptides from certain pathogenic bacteria may be used to stimulate T cells against cancer cells and could hold promise for personalised tumour vaccination approaches. 

Inducing Self-Destruction in Glioblastoma  In this study, researchers have described a class of compounds which are able to cross the blood brain barrier (BBB) to sensitise glioblastoma cells to temozolomide (TMZ)-based chemotherapy. IRE1 is a pro-survival signalling mediator which helps cells overcome stressors, such as TMZ, which makes it an attractive therapeutic option in oncology. Z4P is a IRE1 inhibitor and is able to cross the BBB to stop IRE1 signalling in a mouse model of glioblastoma. The research, published in iScience reported that the treatment of glioblastoma tumours in vivo with a combination of both Z4P and TMZ resulted in improved efficacy and prevented tumour relapse. 

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