PET imaging helps determine whether PD-1 tumor immunotherapy is effective

PD-1 is a protein on T cells and an important immunosuppressive moleculeA growing number of anticancer drugs are designed to suppress PD-1, induce patients' T-cells to attack and kill cancer cellsPD-1 inhibitors such as Pembrolizumab (Keytruda) have helped treat a wide range of cancers, including melanoma, non-small cell lung cancer, kidney cancer, bladder cancer and head and neck cancerbut these drugs are not unfavorable, because not everyone's tumors respond to PD-1 inhibition in the same way, so they are not effective for everyone"the problem with immunotherapy is that it's hard to track reactions, so it's hard to assess whether they're effective," said DrMohammad Rashidian of Boston Children's HospitalWhy is it hard to track? To some extent, in metastatic cancer, there may be many lesions in different parts of the body, and tumor cells can also exist in different formsTo assess the efficacy, the researchers said they couldn'tthere's no way to solve it? Ding, Mohammad Rashidian's team thought - using PET imaging could see if a particular tumor lesion symmothes responded to treatmentThe findings were published in the Proceedings of the National Academy of Sciences (PNAS)https://doi.org/10.1073/pnas.1905005116
The cd8-T cellpractice is the only criterion for testing truthRashidian and his colleagues used a very small antibody fragment (nanobody) in a mouse model of colorectal cancer, which is mainly present in CD8-T cells( also known as killer T cells)When PD-1 is suppressed, CD8-T cells are activated and nanobodies carry radioactive markers that are shown in PET imagingThe team was able to observe how CD8-T cells responded to the treatmentThey scanned about 100 mice with colon cancer with PET enlarged PET image shows colon tumors, which contract after treatment with PD-1 blockers Yellow indicates that CD8-T cells are immersed in the tumor The white border shows the edge of the tumor Photo Source: Mohammad Rashidian /Boston Children's Hospital Rashidian: "If the animal seisced, the CD8-plus cells would expand and move from the periphery to the tumor core This allows you to see the tumor shrink target tumor microenvironment the team explored how PD-1 inhibitors affect the entire tumor "microenvironment", including immune cells responsible for devouring dead and dying tumor cells They sequenced each cell's single-cell RNA to see which genes were turned on or off "We wantto know how the immune system changes in tumors that respond to PD-1 inhibitors," Rashidian said found that in mice that responded to PD-1 inhibitors, the environment around the tumor became more "severe." For example, macrophages (an immune cell) have been transformed into a more "tumor-resistant" state, secreting more signals to help activate CD8-plus cells nanoantibodies are not new concepts
in fact, the concept of nanoantibodies is not new As early as April, Dr Hidde Ploegh, a senior researcher on the study, used similar nanoantibodies ("nanoantibodies" naturally produced from alpacas, camels and jaguars) to enhance the immunity of CAR-T cells to solid tumors The findings were also published in the journal PNAS CAR-T is particularly effective for blood cancer stoic cancer by genetically engineering the patient's own T-cells to better attack cancer cells But CAR-T cells are not very good at eliminating solid tumors, and it is difficult to find cancer-specific proteins that can be safe targets on solid tumors At the same time, solid tumors are also protected by extracellular matrix, and T-cell attacks are weakened by immunosuppressive molecules https://doi.org/10.1073/pnas.1817147116 In this study, researchers implanted nanobodies into CAR-T cells that target specific proteins in the tumor environment The results showed that engineered T-cells killed tumor cells, significantly slowing tumor growth and prolonging the life span of mice with melanoma and colon cancer the Ploegh team believes that the technology itself can be further developed Nanoantibodies may carry a cytokine to enhance the immune response to tumors, and there is much to be done in many solid tumors in the future references: s1 s- PET sies show if PD-1 immuno cancertherapy is working 2 s'nanobodies' from alpacas can bring bring car T-cell therapy to solid tumors