Abstract:
I mmunotherapy has finally been approved as a mainstream modality. Unfortunately, whereas dramatic increases in survival have been achieved, the majority of patients do not yet benefit. It is becoming evident that patients with systematically raised inflammatory markers do not benefit. Furthermore, tumours without evidence of immune cell infiltration and activation are also unlikely to be responders. In order to enhance and increase the number of responders to the standard immune oncology (1-0) agents such as the checkpoint inhibitors (“CPI’s”), it is necessary to activate the innate immune system within the tumour and reduce systemic inflammation. Numerous drugs can reduce inflammation and those cells in the tumour micro environment (TME) that suppress immune responses. These include standard antiinflammatory agents as well as some chemotherapy agents such as Gemcitabine and Cyclophosphamide. Drugs that are capable of enhancing specific immune responses as well as reducing chronic inflammation are known as immune modulators, or “IMiD’s”. These include the Thalidomide analogues such as Lenalidomide and Pomalidomide. Other agents include heat-killed mycobacteria such as mycobacterium obuense, or “IMM-101”. These agents can enhance the immune response to vaccines and CPI’s. Importantly, it is the sequence of these combinations which is key to enhancing efficacy and not just combining all together. More recently, lose dose Naltrexone (LDN) has been shown to be a very effective anti-inflammatory inhibiting TLR9 signaling. Other agents with anti-inflammatory and anti-cancer activity are the cannabinoids which we have shown to enhance radiotherapy and some chemotherapies.
