Short summary

The immune system, e.g. NK cells, play an important role in the fight against cancer. Understanding NK cell function and regulation during oncological treatment is needed in order to improve the overall clinical impact of the markers. We speculate that NK cell activity and regulators of the NK cells (MICA, MICB and TGF- β), levels of PD-1 and PD-L1 assessed in blood samples may identify early treatment failure in patients receiving first-line triplet treatment for mCRC.

Rationale

Colorectal cancer (CRC) is one of the most common types of cancer in the world and the third most common in Denmark with approximately ,4800 new cases each year. The CRC diagnosis is generally related to considerable morbidity and the overall 5-year survival is only around 65%. The number of new cases has increased since the initiation of screening in Denmark in 2014. About 20% of the patients have metastatic disease at the time of diagnosis.

Cancer cells are defined by their ability to grow and divide uncontrolled, spread invasively to surrounding tissues, and disseminate and give rise to metastases by different mechanisms often referred to as hallmarks of cancer. Multiple studies indicate that the immune system also plays a major role in the development of cancer, and our understanding of the critical interactions between the immune system and disease is constantly growing.

The immune system is divided into the innate and the adaptive immune system. The innate immune system plays a primary role in the early response against invading microbial infections but also against aberrant cells such as malignant cancer cells. It comprises several cell types including; natural killer (NK) cells, monocytes and macrophages, dendritic cells, and granulocytes, which all function by identifying and eliminating pathogens and orchestrating the adaptive immune system.

The immune system, and especially NK cells, play an important role in the fight against cancer and may impact the overall benefit derived from oncological treatment. It is currently unknown which cells of the immune system are responsible for tumor shrinkage during treatment and whether the intratumoral coordination between the immune cells differs according to treatment modality. A better understanding of NK cell function and regulation during oncological treatment is needed in order to improve the overall clinical impact of the markers. It is conceivable that increased knowledge about the role of the immune cells and their regulators will lead to a more individualised treatment approach and may guide future immune-related approaches.

We speculate that NK cell activity and regulators of the NK cells (MICA, MICB and TGF- β) and furthermore the levels of PD-1 and PD-L1 assessed in blood samples may identify early treatment failure in patients receiving first-line triplet treatment for mCRC.

Description of the cohort

A retrospective study based on two approved studies conducted at the Department of Oncology, Vejle Hospital. One randomized clinical phase II trial addressing the addition of tocotrienol or placebo to chemotherapy (Folfoxiri) for mCRC and another study monitoring the dynamics of genetic mutations in the plasma of patients receiving standard chemotherapy combined with targeted treatment (anti-EGFR) for metastatic CRC.

Data and biological material

For the total cohort in this study we have collected blood samples.

Clinical data and blood samples is already collected and planned for analysis.

Collaborating researchers and departments

Department of Oncology, Vejle, Lillebaelt Hospital

• Associate professor Torben Frøstrup Hansen, MD, PhD
• Associate professor Lars Henrik Jensen, MD, PhD

Department of Clinical Immunology and Biochemestry, Vejle, Lillebaelt Hospital

• Line Nederby, Molecular Biologist, PhD