Immunomodulation in Patients Receiving Systemic Anti- Cancer Therapy

The use of immunotherapy to treat cancer is a rapidly expanding field. Over the last ten years, the number of clinical trials of immunotherapy, both alone and in combination with other agents, including cytotoxic chemotherapy, has grown exponentially. While the use of immunotherapy has revolutionised the management of cancers such as melanoma, renal cell carcinoma and lung cancer, other diseases, including colorectal cancer, have fared less well. In going forward, an increased understanding of the mechanism of immunotherapy in cancer patients is a vital step in being able to exploit these drugs in cancers where clinical efficacy has previously been limited. Better understanding of immune responses in these patients may identify potential responders to novel immunotherapy. To this end, we developed and validated a panel of immune functional assays, which can be used in clinical trials to assess the immune response in peripheral blood. This panel can therefore be used to gather translational data from clinical trials of anti-cancer therapy. We used these assays to analyse the peripheral blood immune response in patients with metastatic colorectal cancer undergoing first-line chemotherapy, with reference to the neutrophil lymphocyte ratio (NLR). Analysis of samples from 29 patients revealed that, in patients with a high NLR prior to treatment, there was evidence of an attenuated immune response, with increased levels of certain immunosuppressive cytokines and depressed NK cell function. Over the course of treatment, we demonstrated that chemotherapy could partially reverse this phenomenon, potentially enhancing anti-tumour immunity. Similarly, we interrogated blood samples of patients with metastatic melanoma receiving immune therapy with checkpoint inhibitors. Here, we observed evidence of a more active immune response, highlighting the differences between the two patient groups (those with colorectal cancer and those with melanoma). In conclusion, we confirmed that our functional immune assay panel can be used effectively in different groups of cancer patients undergoing a variety of treatments, with the aim of an improved understanding of the immune system in cancer, response to therapy and how this may be exploited in the development of novel treatment strategies.