scholarly journals Case Report: Response to Immunotherapy, Can Radiotherapy Be a Troublemaker?

2021 ◽  
Vol 12 ◽  
Author(s):  
Patricia Martin-Romano ◽  
Julien Adam ◽  
Jean-Yves Scoazec ◽  
Sébastien Gouy ◽  
Antonin Levy ◽  
...  
Keyword(s):  
Immune Response ◽  
Case Report ◽  
Cell Carcinoma ◽  
Immune Microenvironment ◽  
Extensive Analysis ◽  
Immune Contexture ◽  
Previously Treated ◽  
Potential Impact ◽  
Tumor Types ◽  
The Impact

Immunotherapy has dramatically changed the treatment landscape for several tumor types. However, the impact of previous radiotherapy (RT) on response to immunotherapy is still unknown. We report the case of a 58-year-old female diagnosed with a squamous anal cell carcinoma previously treated with RT and having a dissociated response to anti-PD1 agent. An extensive analysis of the immune contexture performed on the tissue collected from both previously RT-treated and RT-untreated lesions confirmed differences on immune microenvironment, highlighting the potential impact of radiotherapy on the immune response.

Squamous Cell Carcinoma in Solitary Laryngeal Papilloma

1980 ◽  
Vol 88 (6) ◽  
pp. 745-748 ◽  
Author(s):  
Milton G. Yoder ◽  
John G. Batsakis
Keyword(s):  
Squamous Cell Carcinoma ◽  
Case Report ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
White Woman ◽  
Malignant Degeneration ◽  
Malignant Neoplasms ◽  
Laryngeal Papilloma ◽  
Previously Treated ◽  
Squamous Cell Papilloma

This case report of a 20-year-old white woman is the youngest patient with a documented squamous cell carcinoma in a solitary nonirradiated laryngeal papilloma. It is rare for malignant degeneration of solitary squamous cell papilloma to occur in a patient under the age of 40. This case is also unique in that most solitary laryngeal papilloma with or without neoplasm occur in males. Most reported malignant neoplasms in squamous papilloma have been previously treated with irradiation. Because approximately 2% to 3% of solitary laryngeal papilloma have malignant neoplasms, adequate biopsy of the lesion and thorough histologic examination must always be done.

The impact of TNFSF14 on prognosis and immune microenvironment in clear cell renal cell carcinoma

2020 ◽  
Vol 42 (9) ◽  
pp. 1055-1066
Author(s):  
Fangshi Xu ◽  
Yibing Guan ◽  
Peng Zhang ◽  
Li Xue ◽  
Xiaojie Yang ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Immune Microenvironment ◽  
Cell Renal Cell Carcinoma ◽  
The Impact

C3 Modulates RBC Antigen to Negatively Regulate Antibody Response

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 22-22 ◽  
Author(s):  
Amanda Mener ◽  
Connie M. Arthur ◽  
Seema R. Patel ◽  
Sean R. Stowell
Keyword(s):  
Flow Cytometry ◽  
Immune Response ◽  
Immune System ◽  
Western Blot ◽  
Antibody Production ◽  
Potential Impact ◽  
The Impact ◽  
Complement Deposition ◽  
Rbc Transfusion ◽  
Over Time

Abstract Background:Red blood cell (RBC) transfusion can result in the development of alloantibodies that can make it difficult to find compatible RBCs for future transfusions and increase the risk of hemolytic transfusion reactions. Despite the consequences of RBC alloimmunization, the factors that regulate this process remain relatively unknown. Recent studies suggest that complement deposition on an antigen surface can significantly enhance the immune response to foreign antigen. As many anti-RBC alloantibodies fix complement and RBCs otherwise lack known adjuvants, early antibody-mediated complement deposition may serve as a key regulator that enhances antibody production. To test this, we employed the KEL RBC model system, which employs RBCs that transgenically express the human KEL antigen specifically on RBCs (KEL RBCs). Using this system, we examined the immunological consequence of KEL RBC exposure following transfusion into C57BL/6 wild-type (WT) or complement component 3 (C3) knockout (KO) recipients. Methods: KEL RBCs were transfused into WT or C3 KO recipients, followed by serum collection on days 3, 5, 7, 14, and 21 post-transfusion. Antibody development in WT or C3 KO recipients was examined by flow crossmatch, where serum was incubated with KEL RBCs followed by antibody detection with fluorescently-tagged secondary anti-IgM and anti-IgG antibodies using flow cytometry. To determine the impact of complement deposition on the level of detectable antigen on the RBC surface, RBCs were labeled with the lipophilic dye, DiI, prior to transfusion and then sampled 1, 2, 3, 5, 7 and 9 days post-transfusion. The level of detectable KEL antigen, complement deposition, KEL RBC survival and antibody bound to the RBC surface was measured by flow cytometry. To examine the effect of complement deposition on the level of KEL protein in the RBC membrane post-transfusion, RBCs stroma was isolated at various time points post transfusion, followed by western blot analysis for the KEL protein. Results: While KEL RBCs induced robust anti-KEL antibody formation and C3 deposition in WT recipients, similar exposure to KEL RBCs in C3 KO recipients actually resulted in an unexpected increase in IgM and IgG anti-KEL antibodies when compared to WT recipients. To determine the consequence of C3 deposition, we examined the potential impact of antibody engagement and complement fixation on KEL antigen levels. Consistent with a potential role for complement in directly impacting KEL antigen availability to the immune system, KEL RBCs transferred into WT recipients experienced a decrease in the level of detectable KEL antigen over time that paralleled the development of anti-KEL antibodies and C3 deposition. In contrast, C3 KO recipients failed to experience the same degree of KEL antigen reduction despite the development of significant anti-KEL antibodies over this same time period. Western blot analysis of RBCs post-transfusion revealed that loss of detectable KEL antigen on the RBC surface paralleled a complete lack of detectable KEL antigen in RBC membranes, indicating that C3 may actually facilitate the removal of KEL from the RBC surface. Conclusion: These results suggest an unexpected role for C3 in negatively regulating antibody responses following RBC transfusion. The impact of C3 on the developing alloantibody response strongly suggests that C3-mediated loss of antigen over time likely reduces antigen availability to the immune system, thereby facilitating the inhibition of antibody production over time. These results not only provide novel insight into potential impact of antigen modulation on the development of an immune response to a RBC alloantigen, but also suggest a completely unexpected role for complement in negatively regulating alloantibody production. In doing so, these results suggest that unique differences in complement activity and overall activation following RBC alloantigen exposure between individuals may represent a previously unrecognized factor that influences alloantibody formation following RBC transfusion. Disclosures No relevant conflicts of interest to declare.

scholarly journals Gene Model Related to m6A Predicts the Prognostic Effect of Immune Infiltration on Head and Neck Squamous Cell Carcinoma

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Yaping Deng ◽  
Kehua Li ◽  
Fengwu Tan ◽  
Hanbo Liu
Keyword(s):  
Immune Response ◽  
Squamous Cell Carcinoma ◽  
High Risk ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Risk Score ◽  
Squamous Cell ◽  
Immune Checkpoint ◽  
Neck Squamous Cell Carcinoma ◽  
Immune Microenvironment

Head and neck squamous cell carcinoma (HNSCC) is a highly aggressive solid tumor. Because most studies have focused on the intrinsic carcinogenic pathways of tumors, we focused on the relationship between N6-methyladenosine (m6A) and the prognosis of HNSCC in the tumor immune microenvironment. We downloaded RNA-seq data from the TCGA dataset and used univariate Cox regression to screen m6A-related lncRNAs. The expression value of LASSO-screened genes was the sum of LASSO regression coefficients. We then evaluated relationships between the risk score and cellular components or cellular immune response. Differences in immune response under various algorithms were visualized with heat maps. The GSVA package in R was used to analyze GO, BP, KEGG, and hallmark gene sets of immune checkpoint clusters and immune checkpoint scores. The GSEA analysis was performed with the cluster profile package, yielding 21 m6A genes. Related lncRNAs were screened with Pearson’s correlations, and the resulting 442 lncRNAs were screened using single-factor analysis. Eight lncRNAs closely related to prognosis were identified through survival random forest. Survival analysis showed that patients with a high risk score had a poor prognosis. Low- and high-risk-score groups differed significantly in m6A gene expression. Prognostic scores from different algorithms were significantly correlated with B cells, T cells, and memory cells in the immune microenvironment. Expression of immune checkpoints and signal pathways differed significantly across risk-score groups, suggesting that m6A could mediate lncRNA-induced immune system dysfunction and affect HNSCC development. A comprehensive study of tumor-cell immune characteristics should provide more insight into the complex immune microenvironment, thus contributing to the development of new immunotherapeutic agents.

scholarly journals Time-synchronized immune-guided SBRT partial bulky tumor irradiation targeting hypoxic segment while sparing the peritumoral immune microenvironment

2019 ◽  
Vol 14 (1) ◽  
Author(s):  
Slavisa Tubin ◽  
Martin Ashdown ◽  
Branislav Jeremic
Keyword(s):  
Immune Response ◽  
Data Analysis ◽  
Response Rate ◽  
Treatment Time ◽  
System Response ◽  
Immune Microenvironment ◽  
Tumor Irradiation ◽  
The Right ◽  
The Impact ◽  
Biomarker Data

Abstract Background A novel unconventional SBRT-based PArtial Tumor irradiation targeting HYpoxic clonogenic cells (SBRT-PATHY) for induction of the tumoricidal bystander (BE) and abscopal effects (AE) was developed by translating our preclinical findings to a clinic in 2016. In order to further improve BE/AE response rate, SBRT-PATHY was upgraded in 2018 by the sparing of peritumoral immune microenvironment as a new OAR, defined by its own dose-constraints. Considering the anti-tumor immune response homeostatic fluctuation, which is cyclically suppressed and incited (“switched off and on”), we synchronized SBRT-PATHY with its most excitable phase, in order to overcome tumor tolerance locally and systemically. The aim of this study, therefore, was to report on the initial results of our latest innovation aimed to further improve BE/AE response rate by testing the effectiveness of the time-synchronized immune-guided SBRT-PATHY. Materials and methods In order to serially map the homeostatic anti-tumor immune response-fluctuations, High Sensitive C-Reactive Protein (HS-CRP), Lactate Dehydrogenase (LDH) and Lymphocyte/Monocyte Ratio (LMR) were analyzed using high-order polynomial trend analysis as surrogate of immune system response. After the biomarker data analysis detected the immune fluctuations and related idiosyncratic immune cycle periodicity, we determined the “most favourable” and “least favourable” treatment time-positions in the immune cycle. In order to evaluate the impact of an idiosyncratic immune cycle on treatment outcomes, our first consecutive four patients were treated on the “most favourable” while the remaining four on the “least favourable” day. Results The median follow-up was 11.8 months. The biomarker data analysis showed periodic immune response fluctuations of regular frequency. The “right” synchronization of SBRT-PATHY with the “most favorable day” of anti-tumor immune response was accompanied with improved clinical outcomes in terms of BE/AE-response rate. Conclusion We believe the right synchronization of radiotherapy with the homeostatically oscillating immune response may improve the probability of inducing BE/AE. Present study has been retrospectively registered on 18th of October 2019 by the ethic committee for Austrian region „Kärnten “in Klagenfurt (AUT), under study number A 37/19.

scholarly journals Bioinformatics and survival analysis of glia maturation factor-γ in pan-cancers

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Aihua Lan ◽  
Chunxia Ren ◽  
Xiaoling Wang ◽  
Guoqing Tong ◽  
Gong Yang
Keyword(s):  
Immune Response ◽  
Cell Carcinoma ◽  
Lung Squamous Cell Carcinoma ◽  
High Expression ◽  
Receptor Interaction ◽  
Lower Grade ◽  
Main Function ◽  
Glia Maturation Factor ◽  
Maturation Factor ◽  
The Impact

Abstract Background Glia maturation factor-γ (GMFG) is reported to inhibit the actin nucleation through binding to the actin-related protein-2/3 complex (Arp2/3). Considering the main function of GMFG in actin remodeling, which is vital for immune response, angiogenesis, cell division and motility, GMFG is supposed to have important roles in tumor development, while up to now, only two studies described the role of GMFG in cancers. By investigating the clinical values of GMFG using The Cancer Genome Atlas (TCGA) data and the functional mechanisms of GMFG through analyses of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichments, this study was aimed to better understand the impact of GMFG in pan-cancers and to draw more attentions for the future research of GMFG. Methods RNA-seq and clinical data of cancer patients were collected from TCGA and analyzed by the Kaplan-Meier methods. GO and KEGG analyses were conducted using the online tools from the Database for Annotation, Visualization and Integrated Discovery (DAVID). Results Compared to the corresponding normal samples, GMFG was significantly upregulated in glioblastoma (GBM), kidney clear cell carcinoma (KIRC), lower grade glioma (LGG), acute myeloid leukemia (LAML), and pancreatic cancer (PAAD), testicular cancer (TGCT), but was downregulated in kidney chromophobe (KICH), lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) (P < 0.05 for all). High expression of GMFG predicted worse OS in GBM (HR = 1.5, P = 0.017), LGG (HR = 2.2, P < 0.001), LUSC (HR = 1.4, P = 0.022) and ocular melanomas (UVM) (HR = 7, P < 0.001), as well as worse DFS in LGG (HR = 1.8, P < 0.001) and prostate cancer (PRAD) (HR = 1.9, P = 0.004). In contrast, high expression of GMFG was associated with better OS in skin cutaneous melanoma (SKCM) (HR = 0.59, P < 0.001) and thymoma (THYM) (HR = 0.098, P = 0.031), as well as better DFS in bile duct cancer (CHOL) (HR = 0.2, P = 0.003). GMFG was mainly involved in the immune response, protein binding and cytokine-cytokine receptor interaction pathways, and was positively associated with multiple immunomodulators in most cancers. Conclusion Our study preliminarily identified that GMFG may cause different survivals for different cancers through modulating tumor progression, immune response status and tissue-specific tumor microenvironment (TME).

scholarly journals The Impact of m1A Methylation Modification Patterns on Tumor Immune Microenvironment and Prognosis in Oral Squamous Cell Carcinoma

2021 ◽  
Vol 22 (19) ◽  
pp. 10302
Author(s):  
Li Gao ◽  
Ru Chen ◽  
Masahiro Sugimoto ◽  
Masanobu Mizuta ◽  
Yo Kishimoto ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Predictive Ability ◽  
Survival Outcomes ◽  
Immune Microenvironment ◽  
Tumor Immune Microenvironment ◽  
The Impact ◽  
Lower Expression

N1-methyladenosine (m1A) modification widely participates in the occurrence and progression of numerous diseases. Nevertheless, the potential roles of m1A in the tumor immune microenvironment (TIME) are still not fully understood. Based on 10 m1A methylation regulators, we comprehensively explored the m1A modification patterns in 502 patients with oral squamous cell carcinoma (OSCC). The m1A modification patterns were correlated with TIME characteristics and the m1A score was established to evaluate the effect of the m1A modification patterns on individual OSCC patients. The TIME characteristics and survival outcomes under the three m1A modification patterns were significantly distinct. OSCC patients in the high m1A score group were characterized by poorer prognosis, lower immune infiltration, lower ssGSEA score, lower expression levels of immune checkpoint molecules, and higher tumor mutation loads. The present study revealed that m1A modification might be associated with the TIME in OSCC, and has potential predictive ability for the prognosis of OSCC.

scholarly journals Survival, Durable Response, and Long-Term Safety in Patients With Previously Treated Advanced Renal Cell Carcinoma Receiving Nivolumab

2015 ◽  
Vol 33 (18) ◽  
pp. 2013-2020 ◽  
Author(s):  
David F. McDermott ◽  
Charles G. Drake ◽  
Mario Sznol ◽  
Toni K. Choueiri ◽  
John D. Powderly ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Overall Survival ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Advanced Renal Cell Carcinoma ◽  
Advanced Treatment ◽  
Previously Treated ◽  
Treatment Refractory ◽  
The Impact

Purpose Blockade of the programmed death-1 inhibitory cell-surface molecule on immune cells using the fully human immunoglobulin G4 antibody nivolumab mediates tumor regression in a portion of patients with advanced treatment-refractory solid tumors. We report clinical activity, survival, and long-term safety in patients with advanced renal cell carcinoma (RCC) treated with nivolumab in a phase I study with expansion cohorts. Patients and Methods A total of 34 patients with previously treated advanced RCC, enrolled between 2008 and 2012, received intravenous nivolumab (1 or 10 mg/kg) in an outpatient setting once every two weeks for up to 96 weeks and were observed for survival and duration of response after treatment discontinuation. Results Ten patients (29%) achieved objective responses (according to RECIST [version 1.0]), with median response duration of 12.9 months; nine additional patients (27%) demonstrated stable disease lasting > 24 weeks. Three of five patients who stopped treatment while in response continued to respond for ≥ 45 weeks. Median overall survival in all patients (71% with two to five prior systemic therapies) was 22.4 months; 1-, 2-, and 3-year survival rates were 71%, 48%, and 44%, respectively. Grade 3 to 4 treatment-related adverse events occurred in 18% of patients; all were reversible. Conclusion Patients with advanced treatment-refractory RCC treated with nivolumab demonstrated durable responses that in some responders persisted after drug discontinuation. Overall survival is encouraging, and toxicities were generally manageable. Ongoing randomized clinical trials will further assess the impact of nivolumab on overall survival in patients with advanced RCC.

Sign in / Sign up

Export Citation Format

Share Document