Linking Transcriptomic and Imaging Data Defines Features of a Favorable Tumor Immune Microenvironment and Identifies a Combination Biomarker for Primary Melanoma.

Patients with resected stage II-III melanoma have approximately a 35% chance of death from their disease. A deeper understanding of the tumor immune microenvironment (TIME) is required to stratify patients and identify factors leading to therapy resistance. We previously identified that the melanoma immune profile (MIP), an IFN-based gene signature, and the ratio of CD8+ cytotoxic T lymphocytes (CTL) to CD68+ macrophages both predict disease-specific survival (DSS). Here, we compared primary with metastatic tumors and found that the nuclei of tumor cells were significantly larger in metastases. The CTL/macrophage ratio was significantly different between primary tumors without distant metastatic recurrence (DMR) and metastases. Patients without DMR had higher degrees of clustering between tumor cells and CTLs, and between tumor cells and HLA-DR+ macrophages, but not HLA-DR- macrophages. The HLA-DR- subset coexpressed CD163+CSF1R+ at higher levels than CD68+HLA-DR+ macrophages, consistent with an M2 phenotype. Finally, combined transcriptomic and multiplex data revealed that densities of CD8 and M1 macrophages correlated with their respective cell phenotype signatures. Combination of the MIP signature with the CTL/macrophage ratio stratified patients into three risk groups that were predictive of DSS, highlighting the potential use of combination biomarkers for adjuvant therapy. SIGNIFICANCE: These findings provide a deeper understanding of the tumor immune microenvironment by combining multiple modalities to stratify patients into risk groups, a critical step to improving the management of patients with melanoma.

Bullous Pemphigoid Associated With a New Combination Checkpoint Inhibitor Immunotherapy

Novel immunotherapies including antibodies to programmed death ligand 1 (PD-1) and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) have become common therapies for neoplasms including metastatic melanoma and non-small cell lung cancer (NSCLC). Dermatologic toxicity is the most common adverse event associated with these immunotherapies. We report a case of bullous pemphogoid (BP) in a patient receiving combination durvalumab and tremelimumab, two newer immunotherapy checkpoint inhibitors under investigation in phase III trials. J Drugs Dermatol. 2019;18(1):103-104.

Correction to: The Role of Oncolytic Viruses in the Treatment of Melanoma.

A correction was made to a sentence in the original article to provide additional clarification in the "Other Oncolytic Viruses" section.

The Role of Oncolytic Viruses in the Treatment of Melanoma.

PURPOSE OF REVIEW: Oncolytic virotherapy is a new approach to the treatment of cancer and its success in the treatment of melanoma represents a breakthrough in cancer therapeutics. This paper provides a review of the current literature on the use of oncolytic viruses (OVs) in the treatment of melanoma. RECENT FINDINGS: Talimogene laherparepvec (T-VEC) is the first OV approved for the treatment of melanoma and presents new challenges as it enters the clinical setting. Several other OVs are at various stages of clinical and pre-clinical development for the treatment of melanoma. Reports from phase Ib-III clinical trials combining T-VEC with checkpoint blockade are encouraging and demonstrate potential added benefit of combination immunotherapy. OVs have recently emerged as a standard treatment option for patients with advanced melanoma. Several OVs and therapeutic combinations are in development. Immunooncolytic virotherapy combined with immune checkpoint inhibitors is promising for the treatment of advanced melanoma.