Sunitinib pretreatment improves tumor-infiltrating lymphocyte expansion by reduction in intratumoral content of myeloid-derived suppressor cells in human renal cell carcinoma.

摘要: Targeted therapy with sunitinib, pazopanib or everolimus has improved treatment outcome for patients metastatic renal cell carcinoma (RCC). However, despite considerable efforts in sequential combined modalities, durable remissions are rare. Immunotherapy like cytokine interleukin-2, T checkpoint blockade adoptive therapies can achieve long-term benefit and even cure. This raises the question of whether combining targeted immunotherapy could also be an effective option RCC patients. Sunitinib, one most frequently administered therapeutics been implicated impairing activation proliferation vitro. In this work, we addressed notion holds true expansion tumor-infiltrating lymphocytes (TILs) sunitinib-treated We compared resected primary tumor material pretreated sunitinib resection specimen from sunitinib-naive found TIL sunitinib-pretreated digests. These products contained more PD-1 expressing TIL, while regulatory infiltration was not altered. The associated reduced intratumoral myeloid-derived suppressor (MDSC) content. Depletion MDSCs tissue-digest expansion, proving functional relevance MDSC alteration by sunitinib. Our vivo results do support previous vitro observations inhibiting function, but provide a possible rationale combination immunotherapy.