Pancreatic Adenocarcinoma is characterized by an immune reaction that is immunosuppressive since the earliest stages of tumor development (Clarck et al., 2007). In a recent article in Science the group leaded by Vonderheide at UPENN investigated the effect of re-activation of the immune response against cancer by the use of CD40 in addition to Gemcitabine in a small group of unresectable pancreatic cancer patients. Encouraging results showed partial response in a number of patients enrolled in this study.
At first sight this confirm the idea that immune therapies should be increasingly tested in controlled studies and eventually become one of the foundation of combination therapies. However when the looked for effective T cell response against tumor in patients and in a Kras and p53 mutated mouse model of pancreatic cancer they didn't observe what they were expecting. What they found instead is a macrophage activation that rapid infiltrated tumor and facilitated depletion of stroma suggesting the immune surveillance was not induced by T cells. This paper follows the revolutionary findings of Tuveson's group (Olive et al, 2009) on the relevance of stroma directed treatments in facilitating drug delivery and anti-tumor efficacy of chemotherapy.
It is exciting to see things coming together in a more comprehensive view of events than we could only imagine a few years ago: novel compounds selectively acting on cancer molecular targets, immune response and microenvironment unveil unanticipated anticancer mechanisms and synergies.
