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Pancreatic cancer chemotherapy is potentiated by induction of tertiary lymphoid structures in mice

A new study has demonstrated that immune cells can be stimulated to assemble into special structures within pancreatic cancer such that, at least in a pre-clinical model, researchers can demonstrate an improvement in the efficacy of chemotherapy (Cell Mol Gastroenterol Hepatol 2021; Research has found that, in some patients with pancreatic cancer, immune cells can assemble into clusters known as tertiary lymphoid structures (TLS) within the stroma, which are associated with improved survival outcomes in patients. However, TLS do not form naturally in all patients with pancreatic cancer. With this in mind, this research team set out to investigate the structure and role of TLS in pancreatic cancer when present, and to evaluate their anti-tumor activity. To determine the presence of TLS within human pancreatic cancer, the team analyzed tissue samples donated by patients to the Pancreatic Cancer Research Fund Tissue Bank. In this study, TLS were defined by the presence of tissue zones rich in B cells, T cells, and dendritic cells-three cell types that have an important role in the immune response. By using specialized staining techniques to visualize the different cell types present within the samples, the team found that TLS were only in a third of patients whose samples were analyzed. To study the development of TLS in pancreatic cancer, the team generated a pre-clinical murine model of pancreatic cancer. TLS were not present in the model initially; however, following the injection of two signaling proteins (known as lymphoid chemokines) into the tumors of the mice, B cells and T cells infiltrated into the tumor site and assembled into TLS. The team then combined the chemokine injection with administration of gemcitabine-a chemotherapy commonly used in the treatment of pancreatic cancer patients. The combination of gemcitabine and chemokine injection resulted in smaller tumors in mice, an effect that was not achieved by either treatment alone. The anti-tumors activity seen after TLS formation in the pre-clinical model was associated with B cells triggering the activation of dendritic cells, which is required for the initiation of an immune response. The findings suggest that lymphoid chemokines, when used in combination with chemotherapy, may represent a viable therapeutic strategy for promoting an anti-tumor immune response that could lead to better clinical outcomes. As this study used a mouse model, further research is now required to determine whether the same outcomes can be observed in other experimental models and in patients. The team believes that a more detailed understanding of TLS formation may aid in the development of personalized therapies that can harness the potential of the body's own immune system to fight cancer.



Multiparametric photoacoustic analysis of human thyroid cancers in vivo

Recently, a joint research team in Korea has proposed a new non-invasive method to distinguish thyroid nodules from cancer by combining photoacoustic and ultrasound image technology with artificial intelligence (Cancer Res 2021; doi: 10.1158/0008-5472.CAN-20-3334). The research team conducted research to acquire photoacoustic images from patients with malignant and benign nodules and analyzed them with artificial intelligence. Currently, the diagnosis of a thyroid nodule is performed using a fine-needle aspiration biopsy (FNAB) using an ultrasound image. But about 20 percent of FNABs are inaccurate, which leads to repetitive and unnecessary biopsies. To overcome this problem, the joint research team explored the use of photoacoustic imaging to obtain an ultrasonic signal generated by light. When light (laser) is irradiated on the patient's thyroid nodule, an ultrasound signal called a photoacoustic signal is generated from the thyroid gland and the nodule. By acquiring and processing this signal, photoacoustic images of both the gland and the nodule are collected. At this time, if multispectral photoacoustic signals are obtained, oxygen saturation information of the thyroid gland and thyroid nodule can be calculated. The researchers focused on the fact that the oxygen saturation of malignant nodules is lower than that of normal nodules, and acquired photoacoustic images of patients with malignant thyroid nodules (23 patients) and those with benign nodules (29 patients). Performing in vivo multispectral photoacoustic imaging on the patient's thyroid nodules, the researchers calculated multiple parameters, including hemoglobin oxygen saturation level in the nodule area. This was analyzed using machine learning techniques to successfully and automatically classify whether the thyroid nodule was malignant or benign. In the initial classification, the sensitivity to classify malignancy as malignant was 78 percent and the specificity to classify benign as benign was 93 percent. The results of photoacoustic analysis obtained by machine learning techniques in the second analysis were combined with the results of the initial examination based on ultrasound images normally used in hospitals. Again, it was confirmed that the malignant thyroid nodules could be distinguished with a sensitivity of 83 percent and a specificity of 93 percent. Going a step further, when the researchers kept the sensitivity at 100 percent in the third analysis, the specificity reached 55 percent. This was about 3 times higher than the specificity of 17.3 percent (sensitivity of 98%) in the initial examination of thyroid nodules using the conventional ultrasound. As a result, the probability of correctly diagnosing benign, non-malignant nodules increased more than 3 times, which shows that overdiagnosis and unnecessary biopsies and repeated tests can be dramatically reduced, and thereby cut down on excessive medical costs.



MRI-targeted or standard biopsy in prostate cancer screening

Most countries have not introduced nationwide prostate cancer screening, as current methods result in overdiagnoses and excessive and unnecessary biopsies. A new study indicates that screening by magnetic resonance imaging (MRI) and targeted biopsies could potentially cut overdiagnoses by half (N Engl J Med 2021 doi: 10.1056/NEJMoa21008522021). Yearly, approximately 1.4 million men get a prostate cancer diagnosis and 375,000 men die from the disease. Previous studies have shown that organized screening can result in earlier detection and thereby reduce the risk of prostate cancer deaths. Current screening methods-prostate-specific antigen (PSA) tests combined with traditional biopsies-result in unnecessary biopsies and the detection of numerous minor low-risk tumors. Consequently, no country except Lithuania has chosen to introduce a nationwide prostate cancer screening program, as the benefits do not exceed the disadvantages. The results of the STHLM3MRI study indicate that overdiagnoses can be halved by substituting traditional prostate biopsies with MRI and targeted biopsies. The number of unnecessary biopsies and the identification of minor low-risk tumors are reduced, while the new method can detect just as many clinically significant tumors. STHLM3MRI is a randomized study conducted between 2018 and 2021 with participants from Stockholm County, which included 12,750 men. The participants first provided a blood sample for PSA analysis, as well as analysis by the new Stockholm3 test, developed by researchers at Karolinska Institute. Men whose tests showed elevated levels were then randomly selected for traditional biopsies or MRI. In the MRI group, biopsies were conducted strictly on suspected tumors identified by MRI. The study proceeded thereafter by investigating how the Stockholm3 test could be combined with MRI to further improve the method for prostate cancer screening.