Immune cell landscape in colorectal cancer from normal mucosa to liver metastasis
Responsible supervisor of the SVOČ project: Andriy Trailin, MD, DSc, andriy.trailin@lfp.cuni.cz
Brief description of the SVOČ project:
Most cancer deaths occur when cancer moves from the original tumor to other organs, which is frequently the liver in case of colorectal cancer (CRC). Metastatic traits of the original tumor can occur either from cell-autonomous mutational changes in the genome of cancer cells or through the exposure to signals from the tumor microenvironment. Resident and infiltrating innate and adaptive immune cells play important role in tumor microenvironment, and altogether can contribute to tumor suppression or promotion. Previous studies have focused on immune microenvironment in the primary tumor, but disregarding the liver metastasis may miss important prognostic information. Density of CD3+ and CD8+ T-cells in primary CRC have demonstrated positive correlation with patient survival. The mechanisms of linkage and coordination of immune response between primary and metastatic tumors remains unestablished and is the focus of this project.
In the current project we use a unique collection of tissue samples from the same patients, including their normal colonic mucosa, a primary CRC sample and a sample from the liver metastasis. For some patients the liver metastases were found at diagnosis, and were collected along with the primary tumor; for other patients the metastases appeared later and matched with the primary tumor. Tissues will be subjected to extensive immunohistochemistry study followed by computer-assisted image analysis aimed at establishing location, densities and functional orientation of innate and adaptive immune cells.
By comparing the immune cell landscape between normal mucosa, primary and metastatic CRC and correlating the findings with pathological and clinical variables, the goal is to understand the role of the patient’s own immune defence in the metastatic process. We will also compare these triplet tissue sets from patients with and without distant metastases at diagnosis in order to show the distinction between immune cell landscape when metastatic process has already taken place to cases when it will take place in the future.
2 students, optimal frequency is 2 times per week, however, remote work is possible.
Results will be presented on students’ scientific conference. Considering the extent and quality of scientific contribution students might be acknowledged in the paper or become co-authors.
Clinic of Infectious Diseases and Travel Medicine. HIV Centre
Responsible supervisor of the SVOČ project: doc. MUDr. Dalibor Sedláček, CSc.
Long-term monitoring of patients’ adherence to antiretroviral treatment
Brief description of the SVOČ project:
Antiretroviral therapy (ART) together with preventive measures are the only recognized methods to control the HIV/AIDS epidemic. Patients on modern ART regimens are regularly monitored and screened at HIV centres. This allows for rapid intervention in the therapeutic regimen should HIV resistance to the drugs being administered develop. It is well known that new ART is well tolerated and has minimal AEs, therefore treatment outcomes are generally very favourable and within about 1-2 months the initial HIV viremia drops to undetectable levels. For the infected person, this means the cessation of HIV replication and restoration of the immune system. A person with an undetectable viral load (VL) is also virtually non-infectious to the environment, which of course has important epidemiological consequences. However, if patients do not adhere to the necessary recommendations (have poor adherence to treatment), then we usually encounter a slow decline in VL and an inadequate immune system response. Monitoring adherence is difficult, but there are laboratory methods that can help us to prove lack of adherence. In additionally educated patients, this often means a positive adherence to treatment and a significant improvement in treatment outcomes.
Students would process patient data and compare laboratory test results with medical records. Evaluation of the parameters monitored will give an overview of adherence. The results obtained from patients on different treatment regimens can be compared, which can help in selecting the optimal therapeutic approach for different groups of patients.
Number of students who could participate in the SVOČ project: 2-3, HIV centre pav. 2, FN Plzeň Bory. Schedule: one 2-3 hours per week