scholarly journals Autoimmune colitis and neutropenia in adjuvant anti-PD-1 therapy for malignant melanoma: efficacy of Vedolizumab, a case report

2022 ◽  
Vol 13 ◽  
pp. 204062232110630
Author(s):  
Maria d’Apolito ◽  
Rocco Spagnuolo ◽  
Maria Anna Siciliano ◽  
Vito Barbieri ◽  
Cristina Cosco ◽  
...  

Immune checkpoint inhibitors (ICIs) represent an important advance in the adjuvant treatment of patients with high-risk melanoma. Although the safety profile of anti-programmed cell death protein-1 (PD-1) is fairly acceptable, different immune-related adverse events (irAEs) are described. Herein we report for the first time a notably multidisciplinary combined approach on a malignant melanoma (MM) patient treated with anti-PD-1 antibody in adjuvant setting. In this novel approach, corticosteroid-refractory immune-mediated colitis (IMC) was effectively treated with Vedolizumab, a selective blockade of the α4β7 integrin and corticosteroids were successfully administered for autoimmune neutropenia. Notably, our patient also express HLA-B*35, a potential biomarker for predicting a genetic basis of autoimmune susceptibility. Our experience offers a possible future perspective about the use of Vedolizumab together with immunotherapy in a strategic early approach for high-risk patients genotyped for HLA.

2021 ◽  
Vol 28 (3) ◽  
pp. 2040-2051
Author(s):  
Christina W. Lee ◽  
J. Gregory McKinnon ◽  
Noelle Davis

Introduction: There are a lack of established guidelines for the surveillance of high-risk cutaneous melanoma patients following initial therapy. We describe a novel approach to the development of a national expert recommendation statement on high-risk melanoma surveillance (HRS). Methods: A consensus-based, live, online voting process was undertaken at the 13th and 14th annual Canadian Melanoma Conferences (CMC) to collect expert opinions relating to “who, what, where, and when” HRS should be conducted. Initial opinions were gathered via audience participation software and used as the basis for a second iterative questionnaire distributed online to attendees from the 13th CMC and to identified melanoma specialists from across Canada. A third questionnaire was disseminated in a similar fashion to conduct a final vote on HRS that could be implemented. Results: The majority of respondents from the first two iterative surveys agreed on stages IIB to IV as high risk. Surveillance should be conducted by an appropriate specialist, irrespective of association to a cancer centre. Frequency and modality of surveillance favoured biannual visits and Positron Emission Tomography Computed Tomography (PET/CT) with brain magnetic resonance imaging (MRI) among the systemic imaging modalities available. No consensus was initially reached regarding the frequency of systemic imaging and ultrasound of nodal basins (US). The third iterative survey resolved major areas of disagreement. A 5-year surveillance schedule was voted on with 92% of conference members in agreement. Conclusion: This final recommendation was established following 92% overall agreement among the 2020 CMC attendees.


2020 ◽  
Author(s):  
Lei Wu ◽  
Guojun Yue ◽  
Wen Quan ◽  
Qiong Luo ◽  
Dongxu Peng ◽  
...  

Abstract Background: Autophagy is a highly conserved homeostatic process in the human body that is responsible for the elimination of aggregated proteins and damaged organelles. Several autophagy-related genes (ARGs) contribute to the process of tumorigenesis and metastasis of prostate cancer (PCa). Also, miRNAs have been proven to modulate autophagy by targeting some ARGs. However, their potential role in PCa still remains unclear.Methods: An univariate Cox proportional regression model was used to identify 17 ARGs associated with the overall survival (OS) of PCa. Then, a multivariate Cox proportional regression model was used to construct a 6 autophagy-related prognostic genes signature. Patients were divided into low-risk group and high-risk group using the median risk score as a cutoff value. High-risk patients had shorter OS than low-risk patients. Furthermore, the signature was validated by ROC curves. Regarding mRNA and miRNA, 12 differentially expressed miRNAs (DEMs) and 1073 differentially expressed genes (DEGs) were detected via the GEO database. We found that miR-205, one of the DEMs, was negatively regulated the expression of ARG (NKX2-3). Based on STRING analysis results, we found that the NKX2-3 was moderately related to the part of genes among the 6 autophagy-related genes prognostic signature. Further, NKX 2-3 was significantly correlated with OS and some clinical parameters of PCa by cBioProtal. By gene set enrichment analysis (GSEA). Lastly, we demonstrated that the association between NKX2-3 and tumor mutation burden (TMB) and PDCD1 (programmed cell death 1) of PCa.Results: We identified that the six ARGs expression patterns are independent predictors of OS in PCa patients. Furthermore, our results suggest that ARGs and miRNAs are inter-related. MiR-205 was negatively regulated the expression of ARG (NKX2-3). Further analysis demonstrated that NKX2-3 may be a potential biomarker for predicting the efficacy of anti-PD-1 therapy in PCa.Conclusions: The current study may offer a novel autophagy-related prognostic signature and may identify a promising miRNA-ARG pathway for predicting the efficacy of anti-PD-1 therapy in PCa.


2020 ◽  
Vol 14 (3) ◽  
pp. 554-560
Author(s):  
Maria Paparoupa ◽  
Sophie Stupperich ◽  
Lisa Goerg-Reifenberg ◽  
Andreas Wittig ◽  
Frank Schuppert

Immune checkpoint inhibitors (ICIs) have been used as immunotherapeutic agents in several malignancies because of their ability to modify the T cell-mediated response against tumor cells. Dual checkpoint inhibition improves remission rates in patients with metastatic melanoma compared to monotherapy. However, a higher incidence of toxicity, including immune-related colitis, has been reported before. A 54-year-old female was diagnosed with malignant melanoma on her left upper arm. Because of progressive metastatic disease, a rescue therapy with nivolumab (Opdivo®) 1 mg/kg and ipilimumab (Yervoy®) 3 mg/kg was initiated and a clinical and radiological remission was achieved. Two weeks after completing the third cycle of the ICI therapy, the patient presented with persistent hemorrhagic diarrhea, nausea and abdominal pain. A diagnostic colonoscopy revealed multiple ulcerative lesions and hemorrhagic colitis of the sigmoid and rectum. Due to the ongoing treatment with nivolumab and ipilimumab, the diagnosis of a checkpoint inhibitor-induced colitis was made and immunosuppression with local and systemic steroids, such as mesalazine was initiated. In order to achieve a long-lasting steroids reduction, we decided to start with infliximab (Remicade® 5 mg/kg body weight i.v. every 2 weeks). Clinical remission was achieved and prednisolone could be subsequently discontinued. Infliximab, in combination with mesalazine, could successfully induce a long-lasting remission without steroids. The treatment of ICI-induced colitis did not lead to a reoccurrence of malignant melanoma after 2 years of follow-up.


2020 ◽  
Vol 13 (2) ◽  
pp. 659-663 ◽  
Author(s):  
Thuridur Thorsteinsdottir ◽  
Teje Løitegård ◽  
Henrik Mikael Reims ◽  
Alina Carmen Porojnicu

The use of immune checkpoint inhibitors has dramatically improved the chance of surviving malignant melanomas; however, the effect comes at the cost of toxicities that are difficult to predict. Immune-mediated hepatitis is the most common form of liver toxicity, but fatal outcome is uncommon. We report the case of a 70-year-old female with metastatic malignant melanoma who developed severe liver toxicity characterized by bile duct injury and cholestasis. The condition progressed despite potent immunosuppressive treatment, plasmapheresis, and intensive supportive care; and the patient died while still having tumor response.


Author(s):  
Shan Yu ◽  
Yan Wang ◽  
Ke Peng ◽  
Minzhi Lyu ◽  
Fenglin Liu ◽  
...  

Different subtypes of gastric cancer differentially respond to immune checkpoint inhibitors (ICI). This study aimed to investigate whether the Estimation of STromal and Immune cells in Malignant Tumor tissues using Expression data (ESTIMATE) algorithm is related to the classification and prognosis of gastric cancer and to establish an ESTIMATE-based gene signature to predict the prognosis for patients. The immune/stromal scores of 388 gastric cancer patients from TCGA were used in this analysis. The upregulated differentially expressed genes (DEGs) in patients with high stromal/immune scores were identified. The immune-related hub DEGs were selected based on protein-protein interaction (PPI) analysis. The prognostic values of the hub DEGs were evaluated in the TCGA dataset and validated in the GSE15460 dataset using the Kaplan-Meier curves. A prognostic signature was built using the hub DEGs by Cox proportional hazards model, and the accuracy was assessed using receiver operating characteristic (ROC) analysis. Different subtypes of gastric cancer had significantly different immune/stromal scores. High stromal scores but not immune scores were significantly associated with short overall survivals of TCGA patients. Nine hub DEGs were identified in PPI analysisThe expression of these hub DEG negatively correlated with the overall survival in the TCGA cohort, which was validated in the GSE15460 cohort. A 9-gene prognostic signature was constructed. The risk factor of patients was calculated by this signature. High-risk patients had significantly shorter overall survival than low-risk patients. ROC analysis showed that the prognostic model accurately identified high-risk individuals within different time frames. We established an effective 9-gene-based risk signature to predict the prognosis of gastric cancer patients, providing guidance for prognostic stratification.


2020 ◽  
Vol 72 (1) ◽  
pp. e108
Author(s):  
Spencer K. Hansen ◽  
Christopher L. Henry ◽  
Brad R. Grimsley ◽  
Mazin I. Foteh ◽  
Dennis R. Gable

2021 ◽  
Vol 12 ◽  
Author(s):  
Jianhua Wu ◽  
Xueting Ren ◽  
Nan Wang ◽  
Ruina Zhou ◽  
Mengsha Chen ◽  
...  

Background: Long noncoding RNAs (lncRNAs) have been discovered to play a regulatory role in genomic instability (GI), which participates in the carcinogenesis of various cancers, including hepatocellular carcinoma (HCC). We endeavored to establish a GI-derived lncRNA signature (GILncSig) as a potential biomarker and explore its impact on immune infiltration and prognostic significance.Methods: Combining expression and somatic mutation profiles from The Cancer Genome Atlas database, we identified GI-related lncRNAs and conducted functional analyses on co-expressed genes. Based on Cox regression analysis, a GILncSig was established in the training cohort (n = 187), and an independent testing patient cohort (n = 183) was used to validate its predictive ability. Kaplan-Meier method and receiver operating characteristic curves were adopted to evaluate the performance. The correlation between GI and immune infiltration status was investigated based on the CIBERSORT algorithm and single sample gene set enrichment analysis. In addition, a comprehensive nomogram integrating the GILncSig and clinicopathological variables was constructed to efficiently assess HCC patient prognosis in clinical applications.Results: A total of 88 GI-related lncRNAs were screened out and the functional analyses indicated diversified effects on HCC progression. The GILncSig was established using four independent lncRNAs (AC116351.1, ZFPM2-AS1, AC145343.1, and MIR210HG) with significant prognostic value (p < 0.05). Following evaluation with the GILncSig, low-risk patients had significantly better clinical outcomes than high-risk patients in the training cohort (p < 0.001), which was subsequently validated in the independent testing cohort. High-risk group exhibited more immunocyte infiltration including B cells memory, macrophages M0 and neutrophils and higher expression of HLA gene set and immune checkpoint genes. Compared to existing HCC signatures, the GILncSig showed better prognosis predictive performance [area under the curve (AUC) = 0.709]. Furthermore, an integrated nomogram was constructed and validated to efficiently and reliably evaluate HCC patient prognosis (3-years survival AUC = 0.710 and 5-years survival AUC = 0.707).Conclusion: The GILncSig measuring GI and impacting immune infiltration serves as a potential biomarker and independent predictor of HCC patient prognosis. Our results highlight further investigation of GI and HCC molecular mechanisms.


BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Lei Wu ◽  
Wen Quan ◽  
Guojun Yue ◽  
Qiong Luo ◽  
Dongxu Peng ◽  
...  

Abstract Background Autophagy is a highly conserved homeostatic process in the human body that is responsible for the elimination of aggregated proteins and damaged organelles. Several autophagy-related genes (ARGs) contribute to the process of tumorigenesis and metastasis of prostate cancer (PCa). Also, miRNAs have been proven to modulate autophagy by targeting some ARGs. However, their potential role in PCa still remains unclear. Methods An univariate Cox proportional regression model was used to identify 17 ARGs associated with the overall survival (OS) of PCa. Then, a multivariate Cox proportional regression model was used to construct a 6 autophagy-related prognostic genes signature. Patients were divided into low-risk group and high-risk group using the median risk score as a cutoff value. High-risk patients had shorter OS than low-risk patients. Furthermore, the signature was validated by ROC curves. Regarding mRNA and miRNA, 12 differentially expressed miRNAs (DEMs) and 1073 differentially expressed genes (DEGs) were detected via the GEO database. We found that miR-205, one of the DEMs, was negatively regulated the expression of ARG (NKX2–3). Based on STRING analysis results, we found that the NKX2–3 was moderately related to the part of genes among the 6 autophagy-related genes prognostic signature. Further, NKX 2–3 was significantly correlated with OS and some clinical parameters of PCa by cBioProtal. By gene set enrichment analysis (GSEA). Lastly, we demonstrated that the association between NKX2–3 and tumor mutation burden (TMB) and PDCD1 (programmed cell death 1) of PCa. Results We identified that the six ARGs expression patterns are independent predictors of OS in PCa patients. Furthermore, our results suggest that ARGs and miRNAs are inter-related. MiR-205 was negatively regulated the expression of ARG (NKX2–3). Further analysis demonstrated that NKX2–3 may be a potential biomarker for predicting the efficacy of anti-PD-1 therapy in PCa. Conclusions The current study may offer a novel autophagy-related prognostic signature and may identify a promising miRNA-ARG pathway for predicting the efficacy of anti-PD-1 therapy in PCa.


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