To the Editor We read with interest the article by Toulmonde and colleagues1 assessing the efficacy and safety of anti–programmed cell death protein 1 (PD-1) antibody and metronomic cyclophosphamide in patients with advanced soft-tissue sarcomas. We found the rationale of this combination approach interesting and worthy of further investigation, despite their unfavorable clinical data. The choice to measure the PD-1 ligand (PD-L1) as a possible predictive parameter of immunotherapy may partially explain their negative results. In fact, PD-1 expression is clear evidence of lymphocyte activation after recognition of immunogenic, that is, tumor, antigen. Conversely, PD-L1 level may reflect only expression of its production by the tumor or tumor-associated macrophages, which, however, can be activated also and exclusively by necrosis.
Macciò A, Madeddu C. Future Prospects for PD-1 Targeting, Macrophage Infiltration, and IDO Pathway Activation in Patients With Sarcomas. JAMA Oncol. 2018;4(8):1134. doi:10.1001/jamaoncol.2018.0875
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