Melanoma is a highly chemoresistant and metastatic tumor that, in the absence of BRAF mutations, is generally treated with the alkylating agent dacarbazine (DTIC). We discovered that DTIC upregulates the expression of NKG2D ligands on tumor cells, leading to the activation of natural killer (NK) and CD8+ T cells. These observations underscore the immunogenic properties of DTIC and provide a rat...

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dacarbazine/placebo (HR = 0.76 [0.63–0.93]; P = 0.006). Rates of adverse events (AEs) were higher with ipilimu mab/dacarbazine and were consistent with those found in previous studies. Most AEs were immune-based and were responsive to dose interruptions or discontinuations, corticosteroids, or other immunosuppressants. Dr. Wolchok noted that although rates of diarrhea (overall, 35.4%; grade 3–4...

Approved for public release; distribution unlimited. 6 ~017. S(DTIC) to comply with regulatory requirements. It has been given no primary dist ibution other than to DTIC a nd will be available only through DTIC or other reference services such as the National Technical Information |Service (NTIS). The vitw. opinit.s, and/or findings contained in this report are those of the author(sl and. T h i...