Antitumor properties of histamine in vivo

To the Editor:

Yang et al.¹ recently reported that mice with histamine deficiency due to genetic disruption of histidine decarboxylase (HDC) show impaired myeloid cell differentiation. The absence of histamine formation caused accumulation of immature myeloid cells (IMCs), which was accompanied by an increased susceptibility to chemically induced cancer¹. Exogenous histamine reversed the accumulation of tumor-promoting IMCs in Hdc^-/- mice, suggesting a potential benefit of histamine-based therapy in cancers¹, where IMCs are believed to contribute to an unfavorable course of disease². Given the effect of exogenous histamine on IMCs, we were surprised that the authors did not discuss the in vivo effects of histamine on cancer development in animals. As seen in Table 1, histamine is an antitumor agent in several histiotypes of experimental cancer^3,4,5,6,7.

Table 1 Histamine in experimental cancer

The authors also did not mention that histamine has been evaluated in clinical trials in cancer as an inhibitor of immunosuppressive myeloid cells⁸. In metastatic renal cell carcinoma, the addition of histamine to interleukin-2 immunotherapy was reported to reduce the number of intratumoral macrophages⁹, implying an effect on the myeloid compartment resembling the results obtained by Yang et al.¹. Furthermore, histamine is approved for use in 31 European countries and Israel to prevent relapse in acute myeloid leukemia (AML), a disease characterized by the accumulation of immature myeloid cells. The therapeutic use of histamine in AML aims to reduce myeloid cell–induced immunosuppression of cytotoxic lymphocytes^8,10. In light of these previous findings, and considering the results presented by Yang et al.¹, further studies to define mechanisms of relevance to the antitumor properties of histamine in vivo seem highly warranted.