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Effect of chemotherapy treatment on the peripheral immune-cellome in patients with pancreatic cancer

Svensson, Maja LU (2021) KIMM05 20211
Department of Immunotechnology
Abstract
Pancreatic cancer (PC) is a severe disease where only 8% of the patients survive longer than five years. Chemotherapy is the standard treatment option for patients with PC, either in adjuvant or palliative setting, however only 15% of the tumors are resectable. The poor prognosis highlights the need to identify new prognostic biomarkers and novel treatment options to improve patient outcome. This longitudinal study aimed to investigate the role of the circulating immune-cellome, and how it is affected by chemotherapy, in 11 patients diagnosed with PC. Buffy coat samples from before (baseline), after 1 and 3 months of treatment were collected and analyzed with flow cytometry to evaluate changes in immune cell populations during... (More)
Pancreatic cancer (PC) is a severe disease where only 8% of the patients survive longer than five years. Chemotherapy is the standard treatment option for patients with PC, either in adjuvant or palliative setting, however only 15% of the tumors are resectable. The poor prognosis highlights the need to identify new prognostic biomarkers and novel treatment options to improve patient outcome. This longitudinal study aimed to investigate the role of the circulating immune-cellome, and how it is affected by chemotherapy, in 11 patients diagnosed with PC. Buffy coat samples from before (baseline), after 1 and 3 months of treatment were collected and analyzed with flow cytometry to evaluate changes in immune cell populations during chemotherapy. Two antibody panels were developed to explore fluctuations in major immune cell populations as well as different T cell subsets. The findings of this study show that granulocytes increased during treatment, whereas T cells and classical monocytes decreased. The frequency of helper T cells, HLA-DR positive cytotoxic T cells and PD-1 positive cytotoxic T cells also decreased over time. Changes in the cell populations were also related to patient survival, where patients surviving longer than 1 year had a higher frequency of non-classical monocytes and effector memory helper T cells at baseline. The present study provides information about the dynamics of circulating immune cells under the pressure of chemotherapy in patients with PC, and if validated in a larger cohort, the results can become helpful for clinical decision making and improve patient outcome. (Less)
Popular Abstract
Pancreatic cancer has a particularly poor prognosis and 1200 people are affected annually in Sweden and only 8% survive five years after diagnosis. With improved knowledge about immune cells, the body’s own defense against disease, treatments can become better and save more lives.

About one third of the people in Sweden are expected to be diagnosed with cancer at some point in their life, which entails great suffering for patients and their relatives. Pancreatic cancer is difficult to treat because the tumor is usually detected at a late stage when surrounding tissue have been invaded and metastases have already been formed. A few patients, about 15%, can have the tumor removed followed by chemotherapy treatment with the goal to cure... (More)
Pancreatic cancer has a particularly poor prognosis and 1200 people are affected annually in Sweden and only 8% survive five years after diagnosis. With improved knowledge about immune cells, the body’s own defense against disease, treatments can become better and save more lives.

About one third of the people in Sweden are expected to be diagnosed with cancer at some point in their life, which entails great suffering for patients and their relatives. Pancreatic cancer is difficult to treat because the tumor is usually detected at a late stage when surrounding tissue have been invaded and metastases have already been formed. A few patients, about 15%, can have the tumor removed followed by chemotherapy treatment with the goal to cure the disease, but the majority of the patients are treated with chemotherapy only. This is a very tough treatment, and many patients suffer from side effects and have to stop the treatment prematurely as the cancer becomes resistant to the treatment.

New treatments that activate the immune cells to attack the cancer have revolutionized the treatment of several cancer diseases but have not yet proven effective in pancreatic cancer. In order to predict who will benefit from a particular treatment and to develop new treatment options we need to know more about the complex relationship between the immune cells and cancer cells. The aim of this study was to get an overview of how immune cells are affected by chemotherapy and if there is a difference in the immune response to chemotherapy in patients who survive longer than one year compared to patients who survive shorter.

In this study, 11 patients with pancreatic cancer were investigated. Blood samples were drawn before the treatment started (baseline), after one month and after three months of treatment, to study immune cells in blood. The samples were analyzed with flow cytometry where receptors on the surface of the immune cells are marked with fluorescent molecules which allows for identification of different cell types.

The results from my study showed that granulocytes, a cell type associated with inflammation, was increased during the treatment, whereas T cells and classical monocytes, cells involved in fighting the disease, were decreased in the blood. Other more specialized types of T cells were decreased as well. Since T cells can have both a favorable and non-favorable role in fighting the cancer, it is difficult to draw any clear conclusions about what this entails for the patient. Differences in certain cell populations that are beneficial in an immune response against cancer could be seen between patients surviving shorter or longer than one year. The immune response in the blood can therefor play an important role for longer survival, but how remains to be discovered.

This study shows that there is much to unveil about the immune cells in patients with pancreatic cancer. A larger cohort is needed to evaluate several factors that might have an impact on the outcome for patients. There is hope that with increased knowledge about the effects of chemotherapy on the patients, better predictions about the response to treatment can be made. (Less)
Please use this url to cite or link to this publication:
author
Svensson, Maja LU
supervisor
organization
course
KIMM05 20211
year
type
H2 - Master's Degree (Two Years)
subject
language
English
id
9062806
date added to LUP
2021-08-25 16:07:23
date last changed
2021-08-25 16:07:23
@misc{9062806,
  abstract     = {{Pancreatic cancer (PC) is a severe disease where only 8% of the patients survive longer than five years. Chemotherapy is the standard treatment option for patients with PC, either in adjuvant or palliative setting, however only 15% of the tumors are resectable. The poor prognosis highlights the need to identify new prognostic biomarkers and novel treatment options to improve patient outcome. This longitudinal study aimed to investigate the role of the circulating immune-cellome, and how it is affected by chemotherapy, in 11 patients diagnosed with PC. Buffy coat samples from before (baseline), after 1 and 3 months of treatment were collected and analyzed with flow cytometry to evaluate changes in immune cell populations during chemotherapy. Two antibody panels were developed to explore fluctuations in major immune cell populations as well as different T cell subsets. The findings of this study show that granulocytes increased during treatment, whereas T cells and classical monocytes decreased. The frequency of helper T cells, HLA-DR positive cytotoxic T cells and PD-1 positive cytotoxic T cells also decreased over time. Changes in the cell populations were also related to patient survival, where patients surviving longer than 1 year had a higher frequency of non-classical monocytes and effector memory helper T cells at baseline. The present study provides information about the dynamics of circulating immune cells under the pressure of chemotherapy in patients with PC, and if validated in a larger cohort, the results can become helpful for clinical decision making and improve patient outcome.}},
  author       = {{Svensson, Maja}},
  language     = {{eng}},
  note         = {{Student Paper}},
  title        = {{Effect of chemotherapy treatment on the peripheral immune-cellome in patients with pancreatic cancer}},
  year         = {{2021}},
}