Impact of Social Determinants of Health on Melanoma Nodal Surveillance in a Multi-institutional Cohort.

Background: Nodal surveillance (NS) has overtaken completion lymphadenectomy as the preferred management for sentinel node-positive (SLN+) melanoma, but requires frequent exams and nodal ultrasound (US). Social determinants of health (SDoH) may affect US adherence in real-world populations, and evaluation of these potential impacts is needed.

Methods: Adults with SLN+ melanoma diagnosed from July 2017 to December 2019 who received NS at nine cancer centers were identified retrospectively.

Inhibition of UBE2N in regulatory T-cells boosts immunity against cancer.

Regulatory T (Treg) cells prevent autoimmunity and facilitate cancer immune evasion. Depletion of Tregs is a promising cancer therapy, but risks of autoimmune reactions hamper its clinical translation. Here, we demonstrate that temporally induced deletion of Ube2n in Tregs (Ube2n ) of adult mice results in a robust expansion and activation of cytotoxic CD8 T-cells in response to cancer cell challenges, producing a long-lasting survival benefit without autoimmune complications.

Neoadjuvant therapy for melanoma: past, present, and future.

Modern systemic therapy has dramatically improved outcomes for many patients with advanced metastatic melanoma. The success of these therapies has attracted much scientific interest while these therapies have made their way into the treatment of earlier stages of disease. Randomized trials have led to the approval of adjuvant immunotherapy and targeted therapy for resected stage III melanoma.

A lactate-SREBP2 signaling axis drives tolerogenic dendritic cell maturation and promotes cancer progression.

Conventional dendritic cells (DCs) are essential mediators of antitumor immunity. As a result, cancers have developed poorly understood mechanisms to render DCs dysfunctional within the tumor microenvironment (TME). After identification of CD63 as a specific surface marker, we demonstrate that mature regulatory DCs (mregDCs) migrate to tumor-draining lymph node tissues and suppress DC antigen cross-presentation in trans while promoting T helper 2 and regulatory T cell differentiation.

Gli2 Facilitates Tumor Immune Evasion and Immunotherapeutic Resistance by Coordinating Wnt Ligand and Prostaglandin Signaling.

Unlabelled: Therapeutic resistance to immune checkpoint blockade has been commonly linked to the process of mesenchymal transformation (MT) and remains a prevalent obstacle across many cancer types. An improved mechanistic understanding for MT-mediated immune evasion promises to lead to more effective combination therapeutic regimens. Herein, we identify the Hedgehog transcription factor, Gli2, as a key node of tumor-mediated immune evasion and immunotherapy resistance during MT.

Articles from 2022 to 2023 to Inform Your Cancer Practice: Melanoma.

Modern effective systemic therapy for melanoma includes two important classes of treatment: immune checkpoint inhibitors (ICIs), comprising inhibitors of cytotoxic T-lymphocyte antigen 4, programmed cell death receptor 1, and lymphocyte-activation gene 3; and small molecule BRAF/MEK inhibitor therapy. These treatments have revolutionized the management of patients with advanced melanoma and have dramatically improved clinical outcomes. The melanoma treatment landscape continues to evolve as outcome data from completed trials continue to mature and as newer studies begin to report data.

Racial, Ethnic, and Gender Diversity Among Academic Surgical Leaders in the US.

Importance: Surgical department chairs remain conspicuously nondiverse despite the recognized importance of diverse physician workforces. However, the extent of diversity among non-chair leadership remains underexplored.

Objective: To evaluate racial, ethnic, and gender diversity of surgical department chairs, vice chairs (VCs), and division chiefs (DCs) in the US.

Functional reprogramming of peripheral blood monocytes by soluble mediators in patients with pancreatic cancer and intraductal papillary mucinous neoplasms.

Background: Monocytes and monocyte-derived tumor infiltrating cells have been implicated in the immunosuppression and immune evasion associated with pancreatic adenocarcinoma (PDAC). Yet, precisely how monocytes in the periphery and tumor microenvironment in patients with intraductal papillary mucinous neoplasm (IPMN), a precursor lesion to PDAC, change during disease progression has not been defined. Here we functionally profiled the peripheral immune system and characterized the tumor microenvironment of patients with both IPMN and PDAC.

Timing of Adjuvant Immunotherapy in Stage III Melanoma, Does it Matter?

Background: The optimal time to initiate adjuvant immune checkpoint inhibitors (ICI) following resection remains undefined. Herein, we investigated the impact of time to adjuvant ICI on survival in patients with stage III melanoma.

Methods: Patients with resected stage III melanoma receiving adjuvant immune therapy were identified within a multi-institutional retrospective cohort.

Survey Study of Clerkship Curriculum on Learner's Choice to Pursue Surgery: Positive Impact of Extracurricular Opportunities.

Objective: Prior studies have focused on the role of the learning environment on students' decisions to pursue surgery, but few have analyzed the impact of the clerkship curriculum. This study assessed surgical clerkship curricula across United States (US) medical schools and their impact on students' likelihood of pursuing a surgical residency.

Design: A cross-sectional survey was developed to assess surgery clerkship characteristics.

At the Intersection of Intersectionality: Race and Gender Diversity Among Surgical Faculty and Trainees.

Objective: To compare the representation of intersectional (ie, racial/ethnic and gender) identities among surgical faculty versus medical students.

Background: Health disparities are pervasive in medicine, but diverse physicians may help the medical profession achieve health equity.

Methods: Data from the Association of American Medical Colleges for 140 programs (2011/2012-2019/2020) were analyzed for students and full-time surgical faculty.

A SREBF2-dependent gene program drives an immunotolerant dendritic cell population during cancer progression.

Unlabelled: Dendritic cells (cDCs) are essential mediators of anti-tumor immunity. Cancers have developed mechanisms to render DCs dysfunctional within the tumor microenvironment. Utilizing CD63 as a unique surface marker, we demonstrate that mature regulatory DCs (mregDCs) suppress DC antigen cross-presentation while driving T 2 and regulatory T cell differentiation within tumor-draining lymph node tissues.

Intratumor childhood vaccine-specific CD4 T-cell recall coordinates antitumor CD8 T cells and eosinophils.

Background: Antitumor mechanisms of CD4 T cells remain crudely defined, and means to effectively harness CD4 T-cell help for cancer immunotherapy are lacking. Pre-existing memory CD4 T cells hold potential to be leveraged for this purpose. Moreover, the role of pre-existing immunity in virotherapy, particularly recombinant poliovirus immunotherapy where childhood polio vaccine specific immunity is ubiquitous, remains unclear.

Tumor-intrinsic NLRP3-HSP70-TLR4 axis drives premetastatic niche development and hyperprogression during anti-PD-1 immunotherapy.

The tumor-intrinsic NOD-, LRR- and pyrin domain-containing protein-3 (NLRP3) inflammasome-heat shock protein 70 (HSP70) signaling axis is triggered by CD8 T cell cytotoxicity and contributes to the development of adaptive resistance to anti-programmed cell death protein 1 (PD-1) immunotherapy by recruiting granulocytic polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) into the tumor microenvironment. Here, we demonstrate that the tumor NLRP3-HSP70 axis also drives the accumulation of PMN-MDSCs into distant lung tissues in a manner that depends on lung epithelial cell Toll-like receptor 4 (TLR4) signaling, establishing a premetastatic niche that supports disease hyperprogression in response to anti-PD-1 immunotherapy. Lung epithelial HSP70-TLR4 signaling induces the downstream Wnt5a-dependent release of granulocyte colony-stimulating factor (G-CSF) and C-X-C motif chemokine ligand 5 (CXCL5), thus promoting myeloid granulopoiesis and recruitment of PMN-MDSCs into pulmonary tissues.