T cell infiltration has been classically placed under the “hot and cold paradigm” where M2 macrophages play a major role in the immunosuppressive microenvironment of cold tumors.17 M2 tumor-associated macrophages (TAMs) have been associated with resistance to immunotherapy and have been a target for drug development.17 In contrast, bioinformatic analysis has postulated SPP1 macrophages to be distinct from the conventional M1 or M2 dogma, highlighting the need for in vivo data.18 However, there remains a lack of mechanistic insight into their specific role and function within the TME.16 Here, SPP1 is linked to neoplasm.