Publications by authors named "Christine G Lian"
Early detection of melanoma through skin surveillance is critical for preventing metastatic progression. Primary cutaneous melanomas at early stage offer a unique opportunity to uncover fundamental mechanisms of tumor initiation, progression, and immune surveillance, but detailed spatial profiling of early disease remains limited. Here we integrate high-plex cyclic immunofluorescence (CyCIF) imaging, spatial transcriptomics, and conventional histology to identify factors associated with de-differentiation and dermal invasion in early-stage melanomas.
View Article and Find Full Text PDFHuman type 1 conventional dendritic cells contribute to skin transplant rejection.
Am J Transplant
August 2025
The skin is the most immunogenic tissue in transplantation and the most difficult tissue in which to induce immune modulation. Batf3-dependent type 1 conventional dendritic cells (cDC1s) are important in initiating rejection in murine skin transplantation. In humans, the CD141 cDC1 subset is the functional counterpart of the murine Batf3-dependent cDC1s.
View Article and Find Full Text PDFBackground: Face transplant rejection is primarily monitored through skin biopsies, but mucosal tissue may detect immune rejection events missed by skin biopsies.
Methods: We retrospectively reviewed 47 paired mucosal and facial skin biopsies and 37 paired facial skin and sentinel flap biopsies from nine face transplant recipients. Rejection was graded using the 2007 Banff classification.
Preferentially expressed Antigen in Melanoma (PRAME) and Ten-Eleven Translocation (TET) dioxygenase-mediated 5-hydroxymethylcytosine (5hmC) are emerging melanoma biomarkers. We observed an inverse correlation between PRAME expression and 5hmC levels in benign nevi, melanoma in situ, primary invasive melanoma, and metastatic melanomas via immunohistochemistry and multiplex immunofluorescence: nevi exhibited high 5hmC and low PRAME, whereas melanomas showed the opposite pattern. Single-cell multiplex imaging of melanoma precursors revealed that diminished 5hmC coincides with PRAME upregulation in premalignant cells.
View Article and Find Full Text PDFArticle Synopsis
- * Researchers identified a specific gene, ID1, that plays a critical role in the transformation process by affecting gene expression and the morphology of melanocytes, indicating its contribution to the early stages of melanoma.
- * The study's findings suggest that there are clinically undetectable precursors to melanoma that exhibit distinct traits and that targeting these precursors could lead to improved methods for early diagnosis and prevention of the disease.
Article Synopsis
- PRAME and 5hmC are important biomarkers in melanoma, showing an inverse relationship where benign nevi have high 5hmC and low PRAME, while melanomas reverse this pattern.
- Research using various imaging and database analyses indicates that lower levels of 5hmC are linked to higher PRAME levels in both premalignant and malignant melanoma cells.
- The study suggests that TET2 plays a crucial role in regulating PRAME expression through DNA hydroxymethylation, highlighting the importance of epigenetic changes in melanoma development.
Article Synopsis
- - Cancer occurs in a complex environment where malignant cells interact with other cells, necessitating advanced methods to analyze these relationships effectively.
- - The study presents SpatialCells, an open-source software that automates the exploration and characterization of tumor microenvironments using detailed single-cell data.
- - SpatialCells can handle samples with millions of cells, aiding in feature extraction and enabling better understanding of tumor growth, invasion, and metastasis through further analyses and predictions.
Article Synopsis
- Uveal melanoma is a rare and aggressive cancer type that often has mutations in genes GNAQ or GNA11, making it resistant to traditional treatments; researchers tested a new drug, BVD-523, an ERK inhibitor, to evaluate its effectiveness.
- A phase II study was conducted with 25 patients, mainly females around 64 years old, who had metastases primarily in the liver and lungs; the study faced challenges, with inconsistent results in terms of patient response and some experiencing significant toxicities.
- Ultimately, the use of BVD-523 did not show promising results for treating metastatic uveal melanoma, highlighting the need for better treatment options as the drug did not improve patient outcomes significantly, and side effects were
Hypertrophic scarring is a major source of morbidity. Sex hormones are not classically considered modulators of scarring. However, based on increased frequency of hypertrophic scarring in patients on testosterone, we hypothesized that androgenic steroids induce abnormal scarring and developed a preclinical porcine model to explore these effects.
View Article and Find Full Text PDFLymphadenopathy and lymph node rejection following facial vascularized composite allotransplantation.
J Plast Reconstr Aesthet Surg
April 2024
Article Synopsis
- The study investigates the immunological processes related to lymphadenopathy in facial transplant patients, focusing on how donor-derived lymph nodes contribute to these processes after vascularized composite allograft (VCA) transplantation.
- It analyzes clinical and histological data from 9 patients, revealing that those who received donor lymph nodes developed bilateral lymphadenopathy, which resolved over time.
- The findings indicate that an immunological response involving both donor and recipient lymphocytes occurs in the lymph nodes, suggesting a unique rejection mechanism that differs from typical skin rejection in transplant patients.*
Article Synopsis
- Complement-mediated diseases can be treated using specific inhibitors, but traditional systemic approaches may increase infection risk and have limited efficacy due to high levels of complement in circulation.
- Researchers developed a new therapy, an antibody fusion protein (C3d-mAb-2fH), that targets complement activity directly in affected tissues rather than systemic circulation, improving localized treatment.
- Experiments show that this approach effectively inhibits complement in tissue and has demonstrated positive results in models for skin and kidney diseases without causing systemic side effects.
Article Synopsis
- Cancer is a complex environment where cancerous and non-cancerous cells interact, necessitating advanced tools to analyze this intricate landscape using new imaging technologies.* -
- The study presents SpatialCells, an open-source software that allows researchers to analyze and characterize tumor microenvironments using detailed single-cell data.* -
- SpatialCells automates the extraction of important features from large datasets and assists in further analyses, enhancing our understanding of how tumors grow and spread.*
Article Synopsis
- The balance of resident and recruited cells in tissues is crucial for maintaining homeostasis and influencing disease development, and this is studied through advanced techniques that analyze the microenvironment at a cellular level.
- A new high-resolution 3D imaging method combines cyclic immunofluorescence with confocal microscopy to reveal detailed cellular structures and their spatial arrangements, enabling better cell classification and interaction analysis.
- In melanoma research, this approach has uncovered complex interactions between different cell types, enhancing our understanding of tumor progression and immune responses, and allowing for detailed tissue profiling that was previously only possible in lab cultures.
Development and validation of time-to-event models to predict metastatic recurrence of localized cutaneous melanoma.
J Am Acad Dermatol
February 2024
Article Synopsis
- This study focuses on improving risk prediction for metastatic recurrence in patients with stage IIB/IIC melanoma to enhance immunotherapy treatment strategies.
- Researchers analyzed data from 954 patients diagnosed with primary cutaneous melanoma, using machine-learning models to evaluate different recurrence types and their survival outcomes.
- The Gradient Boosting Survival model showed high accuracy in predicting distant recurrences, indicating its potential to identify high-risk patients who could benefit most from immunotherapy, although the study faced limitations due to its retrospective design and single geographic cohort.
Article Synopsis
- * Traditional immune checkpoint blockade (ICB) therapies targeting the PD-(L)1 axis have been largely ineffective, prompting researchers to explore the use of epigenetic modulators for better personalized immunotherapy outcomes.
- * A novel 3D screening platform using patient-derived tumor samples has shown that responses to chemotherapy and immunotherapy correlate with immune cell activity and tumor characteristics, suggesting that combining epigenetic priming with ICB could enhance immune response and offer more effective treatment strategies.
Article Synopsis
- Immune-related adverse events (irAEs) can occur during PD-1 cancer immunotherapy and need more research to understand how they compare to regular autoimmune diseases.
- A study using single-cell RNA sequencing on mice showed that anti-PD-1 therapy caused distinct changes in T cells associated with type 1 diabetes (T1D), leading to differences in cell types and function compared to naturally occurring T1D.
- Findings suggest that blood samples from mice treated with anti-PD-1 can be valuable for monitoring irAEs, as the T cell markers differ from those seen in spontaneous T1D, providing potential insights for patient treatment.
Article Synopsis
- - Vascularized composite allotransplantation (VCA) is a new surgical method that helps treat severe injuries, such as losing limbs or facial injuries, by transplanting various tissue types like skin, bone, and muscle.
- - The body's immune system often rejects VCA grafts, especially those with skin, due to their strong antigenicity, which challenges the balance between accepting and rejecting the transplant.
- - Recent research is uncovering the immune cells involved in graft rejection, aiming to develop targeted therapies that could improve the management of VCA transplant patients and potentially reduce the need for lifelong immunosuppression.
Article Synopsis
- - This study explores how whole-slide CyCIF (cyclic immunofluorescence) imaging can effectively analyze immune cell infiltrates in dermatologic adverse events caused by immune checkpoint inhibitors, showcasing its advantages over traditional immunohistochemistry (IHC).
- - Researchers examined six cases of immune-related skin issues and found that CyCIF offers detailed, single-cell immune profiling compared to the more generalized assessments made by IHC, allowing for better understanding of immune cell behavior.
- - The findings suggest that CyCIF can enhance our comprehension of the immune response in dermatologic adverse events and can be applied to fragile tissues, paving the way for future research on specific adverse effects and their underlying mechanisms.
Article Synopsis
- - Vascularized composite allografts (VCAs), particularly of the face, can suffer from chronic rejection, which occurs over long periods and is not fully understood, as shown by the evaluation of a VCA removed after 88 months.
- - The study revealed that donor-derived CD8-positive T cells infiltrate the graft's arteries, leading to damage in recipient-derived endothelial cells, contributing to arteriosclerosis.
- - Advanced proteomic analysis identified specific proteins linked to activated T cells and macrophages along with pathways related to artery hardening, suggesting a chronic rejection mechanism driven by T cell responses and the graft's vascular environment.
Squamous Cell Carcinoma (SCC) develops in stratified epithelial tissues and demonstrates frequent alterations in transcriptional regulators. We sought to discover SCC-specific transcriptional programs and identified the transcription factor Basonuclin 1 (BNC1) as highly expressed in SCC compared to other tumor types. RNA-seq and ChIP-seq analysis identified pro-proliferative genes activated by BNC1 in SCC cells and keratinocytes.
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