Richard P. Tobin
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View article: Profiling Serum Oxylipin Metabolites Across Melanoma Subtypes and Immunotherapy Responders
Profiling Serum Oxylipin Metabolites Across Melanoma Subtypes and Immunotherapy Responders Open
Background/Objectives: Immunotherapy has significantly improved clinical outcomes for patients with late-stage melanoma, yet a substantial portion of patients fail to respond to these treatments. The variability in responses to immunothera…
View article: Decitabine reverses innate immune gene suppression in rare melanomas
Decitabine reverses innate immune gene suppression in rare melanomas Open
Rare melanoma subtypes, including acral, mucosal, and uveal melanomas, exhibit limited responses to immune checkpoint inhibitors (ICIs), yet the molecular mechanisms of immune resistance remain poorly defined. Here, we performed transcript…
View article: Autophagy Differentially Influences Toll-like Receptor 9 and B Cell-Receptor-Mediated B Cell Expansion, Expression of Major Histocompatibility Class II Proteins, and Antigenic Peptide Presentation
Autophagy Differentially Influences Toll-like Receptor 9 and B Cell-Receptor-Mediated B Cell Expansion, Expression of Major Histocompatibility Class II Proteins, and Antigenic Peptide Presentation Open
B cells contribute to innate and adaptive immunity. In the former, Toll-like receptor (TLR) activation promotes the expansion of inflammatory B cells. In the latter, B cell receptor (BCR) activation results in the production of antibodies …
View article: Pembrolizumab and all-trans retinoic acid combination treatment of advanced melanoma: long-term survival update
Pembrolizumab and all-trans retinoic acid combination treatment of advanced melanoma: long-term survival update Open
Background: Primary analysis of the phase I/II clinical trial combining pembrolizumab with all-trans retinoic acid (ATRA) for patients with metastatic melanoma showed a median progression-free survival (PFS) of 20.3 months and median overa…
View article: Profiling serum oxylipin metabolites across melanoma subtypes and immunotherapy responders
Profiling serum oxylipin metabolites across melanoma subtypes and immunotherapy responders Open
Objectives This study investigates the relationship between serum oxylipin profiles and response to immune checkpoint inhibitor therapy in melanoma subtypes to identify potential metabolic biomarkers for treatment response. Methods In a re…
View article: DDDR-39. PI3 KINASE AND CHECKPOINT INHIBITION: A POTENTIALLY NOVEL THERAPEUTIC STRATEGY FOR GLIOBLASTOMA (GBM)
DDDR-39. PI3 KINASE AND CHECKPOINT INHIBITION: A POTENTIALLY NOVEL THERAPEUTIC STRATEGY FOR GLIOBLASTOMA (GBM) Open
Glioblastoma is the most common and aggressive malignant brain tumor with a median survival of less than 2 years, highlighting the need for more effective therapeutics. Dual pathway synergism between PI3K inhibitors and check-point inhibit…
View article: DNA-PK inhibition enhances neoantigen diversity and increases T cell responses to immunoresistant tumors
DNA-PK inhibition enhances neoantigen diversity and increases T cell responses to immunoresistant tumors Open
Effective antitumor T cell activity relies on the expression and MHC presentation of tumor neoantigens. Tumor cells can evade T cell detection by silencing the transcription of antigens or by altering MHC machinery, resulting in inadequate…
View article: Expanding the landscape of oncogenic drivers and treatment options in acral and mucosal melanomas by targeted genomic profiling
Expanding the landscape of oncogenic drivers and treatment options in acral and mucosal melanomas by targeted genomic profiling Open
Despite advancements in treating cutaneous melanoma, patients with acral and mucosal (A/M) melanomas still have limited therapeutic options and poor prognoses. We analyzed 156 melanomas (101 cutaneous, 28 acral, and 27 mucosal) using the F…
View article: MCL1 inhibition targets Myeloid Derived Suppressors Cells, promotes antitumor immunity and enhances the efficacy of immune checkpoint blockade
MCL1 inhibition targets Myeloid Derived Suppressors Cells, promotes antitumor immunity and enhances the efficacy of immune checkpoint blockade Open
Immune checkpoint inhibitors (ICIs) are now the first-line treatment for patients with advanced melanoma. Despite promising clinical results, many patients fail to respond to these therapies. BH3 mimetics, a novel class of small molecule i…
View article: Clinical presentation of cardiac symptoms following treatment with tumor-infiltrating lymphocytes: diagnostic challenges and lessons learned
Clinical presentation of cardiac symptoms following treatment with tumor-infiltrating lymphocytes: diagnostic challenges and lessons learned Open
In the absence of evidence-based guidelines for the treatment of TIL therapy-associated cardiotoxicity, we provided an overview of literature, case descriptions, and recommendations for diagnosis and management to help physicians in daily …
View article: Dysfunctional states of unconventional T-cell subsets in cancer
Dysfunctional states of unconventional T-cell subsets in cancer Open
Unconventional T cells represent a promising therapeutic agent to overcome the current limitations of immunotherapies due to their universal T-cell receptors, ability to respond directly to cytokine stimulation, and capacity to recruit and…
View article: Polymorphic KIR3DL3 expression modulates tissue-resident and innate-like T cells
Polymorphic KIR3DL3 expression modulates tissue-resident and innate-like T cells Open
Most human killer cell immunoglobulin-like receptors (KIR) are expressed by natural killer (NK) cells and recognize HLA class I molecules as ligands. KIR3DL3 is a conserved but polymorphic inhibitory KIR recognizing a B7 family ligand, HHL…
View article: Lysophosphatidic acid modulates CD8 T cell immunosurveillance and metabolism to impair anti-tumor immunity
Lysophosphatidic acid modulates CD8 T cell immunosurveillance and metabolism to impair anti-tumor immunity Open
Lysophosphatidic acid (LPA) is a bioactive lipid which increases in concentration locally and systemically across different cancer types. Yet, the exact mechanism(s) of how LPA affects CD8 T cell immunosurveillance during tumor progression…
View article: Supplementary table 4 from Targeting MDSC Differentiation Using ATRA: A Phase I/II Clinical Trial Combining Pembrolizumab and All-Trans Retinoic Acid for Metastatic Melanoma
Supplementary table 4 from Targeting MDSC Differentiation Using ATRA: A Phase I/II Clinical Trial Combining Pembrolizumab and All-Trans Retinoic Acid for Metastatic Melanoma Open
Characteristics of patients experiencing clinical benefit
View article: Supplementary Table 5 from Targeting MDSC Differentiation Using ATRA: A Phase I/II Clinical Trial Combining Pembrolizumab and All-Trans Retinoic Acid for Metastatic Melanoma
Supplementary Table 5 from Targeting MDSC Differentiation Using ATRA: A Phase I/II Clinical Trial Combining Pembrolizumab and All-Trans Retinoic Acid for Metastatic Melanoma Open
Representativeness of study participants
View article: Supplementary table 2 from Targeting MDSC Differentiation Using ATRA: A Phase I/II Clinical Trial Combining Pembrolizumab and All-Trans Retinoic Acid for Metastatic Melanoma
Supplementary table 2 from Targeting MDSC Differentiation Using ATRA: A Phase I/II Clinical Trial Combining Pembrolizumab and All-Trans Retinoic Acid for Metastatic Melanoma Open
All adverse events experienced by patients, including those unrelated to treatment
View article: Supplementary Figure S1 from Targeting MDSC Differentiation Using ATRA: A Phase I/II Clinical Trial Combining Pembrolizumab and All-Trans Retinoic Acid for Metastatic Melanoma
Supplementary Figure S1 from Targeting MDSC Differentiation Using ATRA: A Phase I/II Clinical Trial Combining Pembrolizumab and All-Trans Retinoic Acid for Metastatic Melanoma Open
Supplementary figure 1. (A) Changes in other circulating cytokines. Colored box denotes the time when the patients were being treated with ATRA. (B) example gating strategy for CD8+ T cell activation.
View article: Supplementary table 2 from Targeting MDSC Differentiation Using ATRA: A Phase I/II Clinical Trial Combining Pembrolizumab and All-Trans Retinoic Acid for Metastatic Melanoma
Supplementary table 2 from Targeting MDSC Differentiation Using ATRA: A Phase I/II Clinical Trial Combining Pembrolizumab and All-Trans Retinoic Acid for Metastatic Melanoma Open
All adverse events experienced by patients, including those unrelated to treatment
View article: Supplementary table 1 from Targeting MDSC Differentiation Using ATRA: A Phase I/II Clinical Trial Combining Pembrolizumab and All-Trans Retinoic Acid for Metastatic Melanoma
Supplementary table 1 from Targeting MDSC Differentiation Using ATRA: A Phase I/II Clinical Trial Combining Pembrolizumab and All-Trans Retinoic Acid for Metastatic Melanoma Open
Trial inclusion/exclusion criteria
View article: Supplementary Figure S2 from Targeting MDSC Differentiation Using ATRA: A Phase I/II Clinical Trial Combining Pembrolizumab and All-Trans Retinoic Acid for Metastatic Melanoma
Supplementary Figure S2 from Targeting MDSC Differentiation Using ATRA: A Phase I/II Clinical Trial Combining Pembrolizumab and All-Trans Retinoic Acid for Metastatic Melanoma Open
Supplementary figure 2. Changes in other clinical hematologic measures. Colored box denotes the time when the patients were being treated with ATRA. * Denotes p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001.
View article: Supplementary Table 5 from Targeting MDSC Differentiation Using ATRA: A Phase I/II Clinical Trial Combining Pembrolizumab and All-Trans Retinoic Acid for Metastatic Melanoma
Supplementary Table 5 from Targeting MDSC Differentiation Using ATRA: A Phase I/II Clinical Trial Combining Pembrolizumab and All-Trans Retinoic Acid for Metastatic Melanoma Open
Representativeness of study participants
View article: Supplementary Figure S1 from Targeting MDSC Differentiation Using ATRA: A Phase I/II Clinical Trial Combining Pembrolizumab and All-Trans Retinoic Acid for Metastatic Melanoma
Supplementary Figure S1 from Targeting MDSC Differentiation Using ATRA: A Phase I/II Clinical Trial Combining Pembrolizumab and All-Trans Retinoic Acid for Metastatic Melanoma Open
Supplementary figure 1. (A) Changes in other circulating cytokines. Colored box denotes the time when the patients were being treated with ATRA. (B) example gating strategy for CD8+ T cell activation.
View article: Data from Targeting MDSC Differentiation Using ATRA: A Phase I/II Clinical Trial Combining Pembrolizumab and All-Trans Retinoic Acid for Metastatic Melanoma
Data from Targeting MDSC Differentiation Using ATRA: A Phase I/II Clinical Trial Combining Pembrolizumab and All-Trans Retinoic Acid for Metastatic Melanoma Open
Purpose:A phase Ib/II clinical trial was conducted to evaluate the safety and efficacy of the combination of all-trans retinoic acid (ATRA) with pembrolizumab in patients with stage IV melanoma.Patients and Methods:Anti–PD-1 naïve patients…
View article: Supplementary table 1 from Targeting MDSC Differentiation Using ATRA: A Phase I/II Clinical Trial Combining Pembrolizumab and All-Trans Retinoic Acid for Metastatic Melanoma
Supplementary table 1 from Targeting MDSC Differentiation Using ATRA: A Phase I/II Clinical Trial Combining Pembrolizumab and All-Trans Retinoic Acid for Metastatic Melanoma Open
Trial inclusion/exclusion criteria
View article: Supplementary table 3 from Targeting MDSC Differentiation Using ATRA: A Phase I/II Clinical Trial Combining Pembrolizumab and All-Trans Retinoic Acid for Metastatic Melanoma
Supplementary table 3 from Targeting MDSC Differentiation Using ATRA: A Phase I/II Clinical Trial Combining Pembrolizumab and All-Trans Retinoic Acid for Metastatic Melanoma Open
Establishing recommended phase II dose (RP2D) and dose limiting toxicities (DLTs)
View article: Supplementary table 4 from Targeting MDSC Differentiation Using ATRA: A Phase I/II Clinical Trial Combining Pembrolizumab and All-Trans Retinoic Acid for Metastatic Melanoma
Supplementary table 4 from Targeting MDSC Differentiation Using ATRA: A Phase I/II Clinical Trial Combining Pembrolizumab and All-Trans Retinoic Acid for Metastatic Melanoma Open
Characteristics of patients experiencing clinical benefit