Delineating the local and systemic immune responses during pancreatic cancer evolution

Projekt: Avhandling



Pancreatic cancer (PC) is a highly lethal disease with nearly paralleling incidence and mortality
rates. It is the most common tumor among a heterogeneous group of neoplasms arising in the
periampullary region, including tumors originating in the distal bile duct, pancreas, ampulla of
Vater or the periampullary duodenum. Only 15-20% of the tumors are resectable at presentation,
and for the remaining 80-85 % the situation is palliative. Treatment options are limited and there is
a profound lack of complementary diagnostics. In addition, despite an increasing armament of
successful systemic therapies, tumor response is often transient. Tumors evolve, like living
organisms, continuously adapting to selective pressures, such as chemotherapy treatment, thus
promoting the emergence of resistant clones with differing effects on the inflammatory tumor
microenvironment. Immune host responses have been shown to correlate with molecular
characteristics of PC and are integral to anti-cancer adaptions, not only for preventing but also for
directing and retarding the evolution of life-threatening malignant cells. However, paradoxical
relationships occur between the immune system and cancer cells, where the immune system
promotes tumor growth both locally and systemically. A hallmark of PC is the presence of an
abundant desmoplasmic stroma consisting of a variety of cancer-associated fibroblasts (CAF) and
immune cells. The CAFs can have either tumour-promoting or tumour-suppressing properties and,
thus far, novel therapies targeting the PC stroma have not been successful in humans.
Gällande start-/slutdatum2022/01/012026/01/01