Summary from 2018 Research Grant Recipient
Report from Soiseck Mesnage, March 2019.
Project Title: Evaluation of the immune profile in sequential tumour samples of patients with ovarian cancer.
Funder: Graci Foundation, The Gynaecological Cancer Research Trust
SUMMARY OF PROJECT UPDATE
Women with ovarian cancer usually present with advanced, incurable disease. Most ovarian cancers are initially sensitive to chemotherapy, however a small subset of ovarian cancers called clear cell ovarian cancers are generally resistant to chemotherapy from the time of diagnosis. A promising new approach for these patients is immunotherapy aimed to help a patient’s own immune system to fight against cancer. In early phase clinical trials of anti-PD-1 immunotherapy, there have been very good responses in a few patients with clear cell ovarian cancer, while others do not respond. To improve outcomes for patients with ovarian cancer, we need ‘biomarkers’ or tests that will help us to better identify which patients would benefit from immunotherapy. We also need a more in-depth understanding of how a patient’s immune system responds to the cancer throughout the disease course in order to develop new immunotherapies and strategies for applying these treatments.
In this study we are using a technique called immunofluorescence to study the immune profile of the tumour at diagnosis and throughout the disease course, in a small cohort of patient’s with clear cell ovarian cancer. Specifically, we are evaluating the expression of PD-L1 and studying the population of immune cells present around the tumour. The rationale for this is based on studies in other tumour types showing that PD-L1 expression is a potential biomarker for response to anti-PD-1 immunotherapy, therefore patients whose tumours are PD-L1-positive may benefit from immunotherapy.
This study is also exploring the link between the immune and genomic profiles in clear cell ovarian cancers. As well as studying PD-L1 expression and the immune cells in these patient’s tumours we have evaluated their tumour DNA for mutations and their RNA for expression of genes of interest. Studies have demonstrated that patients with a high mutational burden tend to respond better to immunotherapy, therefore evaluating the immune profile and correlating this to genomic data may uncover underlying mechanisms for the link between mutational burden and the anti-tumour immune response.
Preliminary results of the immunofluorescence studies have shown that there are more macrophages and T cells in tumour samples compared with normal ovary. A small percentage of the macrophages are PD-L1-positive and T-cells in clusters are PD-L1 positive, whereas T-cells scattered throughout the tumour tended to be PD-L1 negative. The majority of tumour cells showed low levels of PD-L1 expression. The results of these immune studies will also be correlated to data derived DNA mutations and RNA expression.
These initial results show that the patient’s immune system infiltrates around clear cell ovarian cancers, and that some patients with PD-L1 positive cells may benefit from anti-PD-1 immunotherapy. In patients with PD-L1 negative tumours other immunotherapies and strategies should be explored to manipulate or boost the patient’s own immune system to fight against cancer.
Report from Soiseck Mesnage, March 2019.
Project Title: Evaluation of the immune profile in sequential tumour samples of patients with ovarian cancer.
Funder: Graci Foundation, The Gynaecological Cancer Research Trust
SUMMARY OF PROJECT UPDATE
Women with ovarian cancer usually present with advanced, incurable disease. Most ovarian cancers are initially sensitive to chemotherapy, however a small subset of ovarian cancers called clear cell ovarian cancers are generally resistant to chemotherapy from the time of diagnosis. A promising new approach for these patients is immunotherapy aimed to help a patient’s own immune system to fight against cancer. In early phase clinical trials of anti-PD-1 immunotherapy, there have been very good responses in a few patients with clear cell ovarian cancer, while others do not respond. To improve outcomes for patients with ovarian cancer, we need ‘biomarkers’ or tests that will help us to better identify which patients would benefit from immunotherapy. We also need a more in-depth understanding of how a patient’s immune system responds to the cancer throughout the disease course in order to develop new immunotherapies and strategies for applying these treatments.
In this study we are using a technique called immunofluorescence to study the immune profile of the tumour at diagnosis and throughout the disease course, in a small cohort of patient’s with clear cell ovarian cancer. Specifically, we are evaluating the expression of PD-L1 and studying the population of immune cells present around the tumour. The rationale for this is based on studies in other tumour types showing that PD-L1 expression is a potential biomarker for response to anti-PD-1 immunotherapy, therefore patients whose tumours are PD-L1-positive may benefit from immunotherapy.
This study is also exploring the link between the immune and genomic profiles in clear cell ovarian cancers. As well as studying PD-L1 expression and the immune cells in these patient’s tumours we have evaluated their tumour DNA for mutations and their RNA for expression of genes of interest. Studies have demonstrated that patients with a high mutational burden tend to respond better to immunotherapy, therefore evaluating the immune profile and correlating this to genomic data may uncover underlying mechanisms for the link between mutational burden and the anti-tumour immune response.
Preliminary results of the immunofluorescence studies have shown that there are more macrophages and T cells in tumour samples compared with normal ovary. A small percentage of the macrophages are PD-L1-positive and T-cells in clusters are PD-L1 positive, whereas T-cells scattered throughout the tumour tended to be PD-L1 negative. The majority of tumour cells showed low levels of PD-L1 expression. The results of these immune studies will also be correlated to data derived DNA mutations and RNA expression.
These initial results show that the patient’s immune system infiltrates around clear cell ovarian cancers, and that some patients with PD-L1 positive cells may benefit from anti-PD-1 immunotherapy. In patients with PD-L1 negative tumours other immunotherapies and strategies should be explored to manipulate or boost the patient’s own immune system to fight against cancer.