Status of the cancer immunotherapy field
Immunotherapy has revolutionized cancer therapy during the last 15 years.
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Still, the 2 most successful types, immune checkpoint inhibition and CAR T-cell therapy, are curative only in selected cancer types and even so in less than 50 % of patients with advanced cancer.
Dendritic cell (DC)-based cancer therapy has been tested altogether in several hundred clinical trials. The current overall conclusion is that safety and patient tolerability have been satisfactory, but therapeutic effects have not met the high hopes and expectations.
We now understand several reasons why the full potential of DC-based immunotherapy has not been realized. One reason is that DCs commonly have been "trained" to attack only one single tumor-associated antigen, thus not taking cancer heterogeneity into account.
Our CryoIT approach tackles this problem by placing immature DCs in the inflammatory cryoablated cancer tissue so that the DCs may detect and process the entire collection of tumor-associated antigens that exist in each tumor.
Our work has identified additional challenges. Textbooks and a large part of the published literature present a dichotomous view of DC differentiation according to which DCs become either tolerogenic or pro-inflammatory.
We have found that, at least in cell culture, all tested maturation protocols lead to DCs expressing both tolerogenic and pro-inflammatory features simultaneously. Better insights and control of molecular pathways that become activated during DC differentiation could generate more potent pro-inflammatory DCs.
Additionally, it is well documented that physiological negative feedback mechanisms are at play in the body to limit immune attacks. DC viability and longevity represent additional challenges that we recently have become aware of. Optimal control of such normal processes might be necessary to make DC-based cancer therapy efficient enough to treat cancer. More molecular and cellular network insights are required to take out the full potential of DC-based therapy.
Our group additionally works on biomarkers in order to obtain more precise results of clinical trials, including ultradeep T-cell receptor sequencing, liquid biopsies and an In vivo-mimicking Ex vivo-model of standardized tissue explants.