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The incidence of pancreatic cancer has been increasing while its 5-year survival rate has not changed in decades. In the era of personalized medicine, immunotherapy has emerged as a promising treatment modality in a variety of malignancies, including pancreatic cancer. This review will discuss the unique pancreatic tumor microenvironment, including the cells and receptors that transform the pancreas from its normal architecture into a complex mix of suppressor immune cells and dense extracellular matrix that allows for the unrestricted growth of cancer cells. Next, we will highlight the recently completed immunotherapy clinical trials in pancreatic cancer. Finally, we will explore the on-going immunotherapy clinical trials and future directions of this engaging and changing field. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and the second most common cause of cancer death worldwide. Current treatment options for patients with intermediate and advanced HCC are limited, and there is an unmet need for novel therapeutic approaches. HCC is an attractive target for immunomodulation therapy, since it arises in an inflammatory milieu due to hepatitis B and C infections and cirrhosis. However, a major barrier to the development and success of immunotherapy in patients with HCC is the liver’s inherent immunosuppressive function. Recent advances in the field of cancer immunology allowed further characterization of immune cell subsets and function, and created new opportunities for therapeutic modulation of the immune system. In this review, we present the different immune cell subsets involved in potential immune modulation of HCC, discuss their function and clinical relevance, review the variety of immune therapeutic agents currently under investigation in clinical trials, and outline future research directions. [ABSTRACT FROM AUTHOR]

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]

Introduction: Optimal approaches to induce T cell infiltration of tumors are not known. Chemokines CXCL9, CXCL10, and CXCL11 support effector T cell recruitment and may be induced by IFN. This study tests the hypothesis that intratumoral administration of IFNγ will induce CXCL9-11 and will induce T cell recruitment and anti-tumor immune signatures in melanoma metastases. Patients and methods: Nine eligible patients were immunized with a vaccine comprised of 12 class I MHC-restricted melanoma peptides and received IFNγ intratumorally. Effects on the tumor microenvironment were evaluated in sequential tumor biopsies. Adverse events (AEs) were recorded. T cell responses to vaccination were assessed in PBMC by IFNγ ELISPOT assay. Tumor biopsies were evaluated for immune cell infiltration, chemokine protein expression, and gene expression. Results: Vaccination and intratumoral administration of IFNγ were well tolerated. Circulating T cell responses to vaccine were detected in six of nine patients. IFNγ increased production of chemokines CXCL10, CXCL11, and CCL5 in patient tumors. Neither vaccination alone, nor the addition of IFNγ promoted immune cell infiltration or induced anti-tumor immune gene signatures. Conclusion: The melanoma vaccine induced circulating T cell responses, but it failed to infiltrate metastases, thus highlighting the need for combination strategies to support T cell infiltration. A single intratumoral injection of IFNγ induced T cell-attracting chemokines; however, it also induced secondary immune regulation that may paradoxically limit immune infiltration and effector functions. Alternate dosing strategies or additional combinatorial treatments may be needed to promote trafficking and retention of tumor-reactive T cells in melanoma metastases. [ABSTRACT FROM AUTHOR]