While the clinical data and some biological explanations have been comprehensively described before [1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17], this review aims to discuss several unexplored questions and mechanisms that may contribute to HP, with a particular focus on tumour-intrinsic PD-1/PD-L1 signalling. The gene discussed is PDCD1; the disease is neoplasm.