Functionally and Metabolically Divergent Melanoma-Associated Macrophages Originate from Common Bone-Marrow Precursors.

Tumor-associated macrophages (TAMs) can be widely heterogeneous, based on their ontogeny and function, and driven by the tissue-specific niche. TAMs are highly abundant in the melanoma tumor microenvironment (TME), usually correlating with worse prognoses. However, the understanding of their diversity may be harnessed for therapeutic purposes.

Functionally and metabolically divergent melanoma-associated macrophages originate from common bone-marrow precursors.

Melanomas display high numbers of tumor-associated macrophages (TAMs), which correlate with worse prognosis. Harnessing macrophages for therapeutic purposes has been particularly challenging due to their heterogeneity, based on their ontogeny and function and driven by the tissue-specific niche. In the present study, we used the YUMM1.

Skin Cancer Incidence in Organ Transplant Recipients Referred for Benign Skin Conditions.

Background: Solid organ transplant recipients (SOTRs) are at ∼100-fold increased risk for developing skin cancers compared with the general population, with increased morbidity and mortality. These patients are closely followed by dermatology; however, it is unclear how referral reasons from nondermatologic providers affect care in these patients.

Objective: This study examines the reason SOTRs are referred to dermatologic care by nondermatologic providers as a potential predictor of nonmelanoma skin cancer (NMSC) outcomes.

Topical arginase inhibition decreases growth of cutaneous squamous cell carcinoma.

Cutaneous squamous cell carcinomas (cSCC) are among the most commonly diagnosed malignancies, causing significant morbidity and mortality. Tumor-associated macrophage (TAM) expression of arginase is implicated in tumor progression, and therapeutic use of arginase inhibitors has been studied in various cancers. However, investigating potential cSCC immunotherapies including arginase inhibition in pre-clinical models is hampered by the lack of appropriate tumor models in immunocompetent mice.

Photoacoustic Imaging of Tattoo Inks: Phantom and Clinical Evaluation.

Photoacoustic imaging (PAI) is a novel hybrid imaging modality that provides excellent optical contrast with the spatial resolution of ultrasound in vivo. The method is widely being investigated in the clinical setting for diagnostic applications in dermatology. In this report, we illustrate the utility of PAI as a non-invasive tool for imaging tattoos.

Ultradeep sequencing differentiates patterns of skin clonal mutations associated with sun-exposure status and skin cancer burden.

In ultraviolet (UV) radiation-exposed skin, mutations fuel clonal cell growth. The relationship between UV exposure and the accumulation of clonal mutations (CMs) and the correlation between CMs and skin cancer risk are largely unexplored. We characterized 450 individual-matched sun-exposed (SE) and non-SE (NE) normal human skin samples.

Ultraviolet imaging in dermatology.

Visual examination plays a central role in the diagnosis of skin diseases. Many dermatologists use magnification, or dermoscopy, to improve diagnostic certainty when assessing the skin under visible light. In addition to magnification, other technological advances have been made over the last century to improve our visual assessment of the skin.

Skin cancer in transplant recipients: Scientific retreat of the international immunosuppression and transplant skin cancer collaborative and skin care in organ transplant patients-Europe.

The International Immunosuppression and Transplant Skin Cancer Collaborative (ITSCC) is an organization of more than 500 physicians and scientists focused on the treatment of cutaneous malignancies following solid organ transplantation and in other forms of immunosuppression. It is well known that solid organ transplant recipients (SOTRs) have an approximate 100-fold increase in the risk of developing skin cancer with consensus guidelines recommending these patients be managed as high risk for local recurrence and metastasis associated with poor outcomes. In September 2018, ITSCC and its European counterpart, the Skin Care in Organ Transplant Patients-Europe (SCOPE), held their biennial scientific retreat in Essex, MA to discuss novel findings in the pathogenesis of cutaneous malignancy including new treatment and prevention strategies in this at-risk population for significant morbidity and mortality from their cutaneous disease.

Human keratinocyte carcinomas have distinct differences in their tumor-associated macrophages.

Unlabelled: Cutaneous squamous cell carcinomas (SCCs) and basal cell carcinomas (BCCs) have different clinical behaviors, despite both being keratinocyte carcinomas mainly caused by ultraviolet radiation. Whether these distinct features are associated with tumor-associated macrophages (TAMs) is largely unknown. The main goal of this study was to conduct a comprehensive analysis of density and polarization states of TAMs in SCCs BCCs.

TLR-3 Stimulation Skews M2 Macrophages to M1 Through IFN-αβ Signaling and Restricts Tumor Progression.

During tumor progression, macrophages shift their protective M1-phenotype to pro-tumorigenic M2-subtype. Therefore, conversion of M2 to M1 phenotype may be a potential therapeutic intervention. TLRs are important pathogen recognition receptors expressed by cells of the immune system.

Cutaneous Squamous Cell Carcinomas in Solid Organ Transplant Recipients Compared With Immunocompetent Patients.

Importance: Solid organ transplant recipients (SOTRs) have a 100-fold increased risk of squamous cell carcinoma (SCC), and they may develop more aggressive SCCs compared with immunocompetent individuals.

Objective: To compare outcomes associated with aggressive behavior of SCC in SOTRs and high-risk immunocompetent patients.

Design, Setting, And Participants: A retrospective cohort study of 58 SOTRs and 40 immunocompetent patients evaluated at the Yale Transplant Dermatology Clinic in New Haven, Connecticut, who had at least 1 SCC confirmed histopathologically between January 1, 2008, and December 31, 2015.

Skin Cancers in Organ Transplant Recipients.

Long-term utilization of immunosuppression in organ transplant recipients (OTRs) leads to decreased immune-mediated tumor surveillance and development of malignant tumors. A delicate balance needs to be maintained in the intensity of immunosuppression to keep the risk of malignancy low without jeopardizing life-saving graft function. OTRs are prone to developing skin cancers that exhibit unique epidemiologic, pathophysiologic, and prognostic characteristics.

Cutaneous Toxicities From Transplantation-Related Medications.

Despite the abundance of information on cutaneous malignancies associated with solid organ transplantation in the transplant literature, there is limited information regarding nonmalignant skin changes after transplantation. There are numerous skin toxicities secondary to immunosuppressive and other transplant-related medications that can vary in presentation, severity, and prognosis. To limit associated morbidity and mortality, solid organ transplant recipient care providers should effectively identify and manage cutaneous manifestations secondary to drug toxicity.

The role of macrophages in skin homeostasis.

The skin and its appendages comprise the largest and fastest growing organ in the body. It performs multiple tasks and maintains homeostatic control, including the regulation of body temperature and protection from desiccation and from pathogen invasion. The skin can perform its functions with the assistance of different immune cell populations.

Incidence of and Risk Factors for Skin Cancer in Organ Transplant Recipients in the United States.

Importance: Skin cancer is the most common malignancy occurring after organ transplantation. Although previous research has reported an increased risk of skin cancer in solid organ transplant recipients (OTRs), no study has estimated the posttransplant population-based incidence in the United States.

Objective: To determine the incidence and evaluate the risk factors for posttransplant skin cancer, including squamous cell carcinoma (SCC), melanoma (MM), and Merkel cell carcinoma (MCC) in a cohort of US OTRs receiving a primary organ transplant in 2003 or 2008.

Myeloid Cell-Derived HIF-1α Promotes Control of Leishmania major.

Hypoxia-inducible factor-1α (HIF-1α), which accumulates in mammalian host organisms during infection, supports the defense against microbial pathogens. However, whether and to what extent HIF-1α expressed by myeloid cells contributes to the innate immune response against Leishmania major parasites is unknown. We observed that Leishmania-infected humans and L.

NLRC4 suppresses melanoma tumor progression independently of inflammasome activation.

Members of the NLR family can assemble inflammasome complexes with the adaptor protein ASC and caspase-1 that result in the activation of caspase-1 and the release of IL-1β and IL-18. Although the NLRC4 inflammasome is known to have a protective role in tumorigenesis, there is an increased appreciation for the inflammasome-independent actions of NLRC4. Here, we utilized a syngeneic subcutaneous murine model of B16F10 melanoma to explore the role of NLRC4 in tumor suppression.

Skin Cancer in the Crosshairs: Highlights from the Biennial Scientific Retreat of International Transplant Skin Cancer Collaborative and Skin Care in Organ Transplant Recipients Europe.

The International Transplant Skin Cancer Collaborative (ITSCC) is an organization comprising of physicians; transplant surgeons and basic science research scientists dedicated in providing optimal care and ongoing research advancements in solid organ transplant recipients to improve patient outcome and quality of life. As medical advances occur, it is anticipated that the sheer number of solid organ transplantations occurring worldwide will continue to increase. The long-term medication associated immunosuppression improves graft survival, but as a consequence, these individuals become increasingly susceptible to various cutaneous malignancies, lymphoproliferative disorders and infections.