Evidence of immune elimination, immuno-editing and immune escape in patients with hematological cancer

AbstractThere is mounting evidence that the immune system can spontaneously clear malignant lesions before they manifest as overt cancer, albeit this activity has been difficult to demonstrate in humans. The calreticulin (CALR) exon 9 mutations are driver mutations in patients with chronic myeloproliferative neoplasms (MPN), which are chronic blood cancers. TheCALR mutations generate a neo-antigen that is recognized by patient T cells, and T cells isolated from a patient with aCALR-mutation can recognize and kill autologousCALR-mutant cells. Surprisingly, healthy individuals display frequent and strong T cell responses to the CALR neo-antigens too. Furthermore, healthy individuals display immune responses to all parts of the mutant CALR epitope, and the CALR neo-epitope specific responses are memory T cell responses. These data suggest that although healthy individuals might acquire aCALR mutation, the mutant cells can be eliminated by the immune system. Additionally, a small fraction of healthy individuals harbor aCALR exon 9 mutation. Four healthy individuals carryingCALR mutations underwent a full medical examination including a bone marrow biopsy after a median follow up of 6.2  years. None of these patients displayed any signs ofCALR-mutant MPN. Additionally, all healthy individuals displayed strong CALR neo-epitope specific T cell responses suggesting that these healthy individuals retained theirCALR-mutant cells in the editing stage for several years. Thus, we suggest...
Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology Source Type: research