An abnormal signal pathway, loss or mutation of tumor suppressor genes, loss or down-regulation of target antigen, JAK1/2, B2M and Apelin receptor gene mutation, TIM/LAG3 expression, inhibitory checkpoint increase, activation checkpoint decrease, T cell depletion, phenotypic changes, tumor microenvironment and drug antigenicity all play important roles in immunotherapy resistance [231,232,233,234,235,236,237,238]. Here, APLNR is linked to neoplasm.