The ability of the immune system to eliminate tumor cells has been proven and well documented over the last two decades. Tumor cells can be eliminated by cytotoxic T cells that recognize tumor antigens, most of which represent mutations that have occurred over time.
Currently there are several types of immunotherapies in development and in clinical use that either target cancer-mediated immune escape mechanism or boost the immune system. These include agonist for dendritic cell activation, cancer vaccines, T-cell therapy and immune checkpoint inhibitors.
New immunotherapies, such as immune checkpoint inhibitors, tend to be most effective on tumors that are T-cell inflamed (hot), whereas those that are not T-cell inflamed (cold) are much less responsive to immunotherapy.
New immunotherapeutic strategies are therefore needed to enhance the presence of T cells in cold tumors and thereby making them more sensitive to immunotherapy.
Challenges in cancer immunotherapy
Even though cancer immunotherapy has revolutionized cancer treatment, still only a minority of cancer patients respond to cancer immunotherapy. The main reasons for low response rate are tumor heterogeneity and immunosuppression.
During tumor growth, new mutations accumulate and result in tumor cells with distinct mutations and different sensitivity to treatment. This cellular diversity of the tumor makes it very challenging to treat as it can develop therapy resistance. In a survey among high prescribers, tumor heterogeneity was ranked as the major hurdle for successful treatment of cancer (GlobalData High-Prescriber Survey, Dec. 2020).
Tumor heterogeneity represents a major challenge to kill all cancer cells in one tumor and to develop cancer therapies that work universally for all kind of tumors. In the case of cancer immunotherapy, tumor heterogeneity is a substantial barrier for successful outcome.