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Introduction: Infiltration of cancers by T cells is associated with improved patient survival and response to immune therapies; however, optimal approaches to induce T cell infiltration of tumors are not known. This study was designed to assess whether topical treatment of melanoma metastases with the TLR7 agonist imiquimod plus administration of a multipeptide cancer vaccine will improve immune cell infiltration of melanoma metastases. Patients and methods: Eligible patients were immunized with a vaccine comprised of 12 melanoma peptides and a tetanus toxoid-derived helper peptide, and imiquimod was applied topically to metastatic tumors daily. Adverse events were recorded, and effects on the tumor microenvironment were evaluated from sequential tumor biopsies. T cell responses were assessed by IFNγ ELIspot assay and T cell tetramer staining. Patient tumors were evaluated for immune cell infiltration, cytokine and chemokine production, and gene expression. Results and conclusions: Four eligible patients were enrolled, and administration of imiquimod and vaccination were well tolerated. Circulating T cell responses to the vaccine was detected by ex vivo ELIspot assay in 3 of 4 patients. Treatment of metastases with imiquimod induced immune cell infiltration and favorable gene signatures in the patients with circulating T cell responses. This study supports further study of topical imiquimod combined with vaccines or other immune therapies for the treatment of melanoma. [ABSTRACT FROM AUTHOR]

Despite surgical treatment of primary tumor, about 5-10 % of melanoma patients will eventually suffer from cutaneous or subcutaneous metastasis. The presence of skin metastases decreases patients' quality of life. Their management is a challenge and depends on several variables such as size and number of the lesions, their location, the presence or absence of visceral metastasis. When possible, radical surgical resection is the best approach; if surgery is not expected to provide a reasonable functional outcome, alternative treatments must be considered. Several local and loco-regional treatments, such as electrochemotherapy and regional chemotherapy, are available for the management of melanoma skin metastasis. Even if high response rates have been observed in several clinical trials, their impact on survival is not clear. Efforts are being made to improve their efficacy and minimize toxicity. The combination of such treatments with immunotherapy could be a strategy to induce durable responses and improve survival. In fact, regionally treated patients do not have the immune suppression associated with most systemic treatments, which could compromise the efficacy of immunotherapy, and recent findings suggest that the inflammatory reactions following loco-regional cytotoxic treatments, such as electrochemotherapy, may enhance the activity of immunotherapeutic agents. In this manuscript, we review recent studies on electrochemotherapy and melanoma skin metastasis, and we comment about the role that combinations with immunotherapy may have based on the data provided by clinical trials and translational research. [ABSTRACT FROM AUTHOR]

The dichotomy of immunology into innate and adaptive immunity has created conceptual barriers in appreciating the intrinsic two-way interaction between immune cells. An emerging body of evidence in various models of immune rejection, including cancer, indicates an indispensable regulation of innate effector functions by adaptive immune cells. This bidirectional cooperativity in innate and adaptive immune functions has broad implications for immune responses in general and for regulating the tumor-associated inflammation that overrides the protective antitumor immunity. Mechanistic understanding of this two-way immune cross-talk could provide insights into novel strategies for designing better immunotherapy approaches against cancer and other diseases that normally defy immune control. [ABSTRACT FROM AUTHOR]

The main aims of the international meeting “Immunotherapy of Cancer: Challenges and Needs” were to review the state of the art of cancer immunotherapy and to identify critical issues which deserve special attention for promoting progress of research in this field, with a particular focus on the perspectives of clinical research. Novel concepts and strategies for identifying, monitoring and predicting effective responses to cancer immunotherapy protocols were presented, focused on the use of adjuvants (CpG oligonucleotides) or cytokines (IFN-alpha) to enhance the efficacy of cancer vaccines. Moreover, the possible advantages of using different types of dendritic cells (for active immunization strategies) or T cells (for adoptive immunotherapy protocols) were debated. A consensus was achieved on the need for enhancing the efficacy of cancer vaccines or adoptive cell immunotherapy by combining these strategies with other anti-cancer treatments, including chemotherapy. Finally, initiatives for promoting clinical research by establishing a strategic cooperation in the field of cancer immunotherapy based on the active participation of all the relevant actors, including public institutions responsible of Public Health, National Cancer Institutes, industry, representatives of regulatory bodies, and patients’ organizations were proposed. [ABSTRACT FROM AUTHOR]