There are several potential reasons why a mutant calreticulin‐directed peptide vaccine might not induce an immune response in patients, including (i) the patients who received the vaccine may not have expressed human leukocyte antigen (HLA) subtypes that present the mutant calreticulin neo‐epitope with high affinity, (ii) defects in major histocompatibility complex (MHC)‐mediated presentation of the mutant calreticulin neo‐epitope, (iii) inadequate immune stimulation by the adjuvant and (iv) an immunosuppressive microenvironment in the context of MPN‐related chronic inflammation. The gene discussed is HLA-C; the disease is myeloproliferative neoplasm.