Pub Date : 2019-08-01DOI: 10.29245/2578-3009/2019/4.1174
V. Jain, Sriram Venigalla, K. Nead, W. Hwang, J. Lukens, T. Mitchell, J. Shabason
Pre-clinical data from animal models suggest that the anti-tumor efficacy of immune checkpoint blockade agents may be influenced by gender specific sex hormones. However, recent meta-analyses of clinical data aimed at addressing the impact of gender on response to these agents have demonstrated conflicting results. Given the discordant evidence, we sought to evaluate the association of gender with the receipt and efficacy of modern immunotherapies in patients with metastatic melanoma. This retrospective cohort study used the National Cancer Database to identify patients who were ≥18 years old with Stage IV melanoma from 2011 to 2015. Patterns of utilization of immunotherapy, including by gender, were assessed using multivariable logistic regression. A multivariable Cox proportional hazards model, including an interaction term between the receipt of immunotherapy and gender, was used to evaluate whether gender modified the association of receipt of immunotherapy with hazards of death. 11,944 patients met study inclusion criteria. Of these, 8,093 (68%) were males and 3,851 (32%) were females. 2,930 (25%) patients received immunotherapy while 9,014 (75%) did not. There was no statistically significant difference in the receipt of immunotherapy between males and females. On multivariable analysis, receipt of immunotherapy was associated with a survival benefit in both males and females. However, a statistically significant difference in efficacy of immunotherapy based on gender was not observed (p interaction =0.422). Utilizing a real world cohort of patients derived from a national cancer registry, gender was not associated with differences in immunotherapy survival outcomes in patients with metastatic melanoma.
{"title":"Association of Gender with Efficacy of Immunotherapy in Metastatic Melanoma","authors":"V. Jain, Sriram Venigalla, K. Nead, W. Hwang, J. Lukens, T. Mitchell, J. Shabason","doi":"10.29245/2578-3009/2019/4.1174","DOIUrl":"https://doi.org/10.29245/2578-3009/2019/4.1174","url":null,"abstract":"Pre-clinical data from animal models suggest that the anti-tumor efficacy of immune checkpoint blockade agents may be influenced by gender specific sex hormones. However, recent meta-analyses of clinical data aimed at addressing the impact of gender on response to these agents have demonstrated conflicting results. Given the discordant evidence, we sought to evaluate the association of gender with the receipt and efficacy of modern immunotherapies in patients with metastatic melanoma. This retrospective cohort study used the National Cancer Database to identify patients who were ≥18 years old with Stage IV melanoma from 2011 to 2015. Patterns of utilization of immunotherapy, including by gender, were assessed using multivariable logistic regression. A multivariable Cox proportional hazards model, including an interaction term between the receipt of immunotherapy and gender, was used to evaluate whether gender modified the association of receipt of immunotherapy with hazards of death. 11,944 patients met study inclusion criteria. Of these, 8,093 (68%) were males and 3,851 (32%) were females. 2,930 (25%) patients received immunotherapy while 9,014 (75%) did not. There was no statistically significant difference in the receipt of immunotherapy between males and females. On multivariable analysis, receipt of immunotherapy was associated with a survival benefit in both males and females. However, a statistically significant difference in efficacy of immunotherapy based on gender was not observed (p interaction =0.422). Utilizing a real world cohort of patients derived from a national cancer registry, gender was not associated with differences in immunotherapy survival outcomes in patients with metastatic melanoma.","PeriodicalId":73785,"journal":{"name":"Journal of immunological sciences","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90622403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-06-01DOI: 10.29245/2578-3009/2019/3.1173
M. Takamori
The neuromuscular junction (NMJ) is organized by a complex architecture and various signals orchestrated by sophisticated interactions. They include the presynaptic Ca2+ homeostasis for acetylcholine (ACh) release in the active zone organization, the post-synaptic ACh receptor (AChR) clustering at endplate membranes, the trans-synaptic communication from muscle to nerve, and the synaptic stabilization. The present data and discussions are concerned in an adaptive change of ACh release from the nerve terminal and its immunological impairment in the post-synaptic disease (myasthenia gravis, MG) and the presynaptic disease (Lambert-Eaton myasthenic syndrome, LEMS). Discussions mainly focus the antibody-induced failure of the synaptic compensatory mechanisms that are brought about by the presynaptic autoreceptors (the M1type muscarinic AChR [mAChR] cooperated with adenosine receptors), and the non-voltage-gated Ca2+-dominant influx channel (transient receptor potential canonical [TRPCs], particularly its phenotype TRPC3). Besides the synaptic transmission fatigue, the TRPC3 antibodies are discussed in terms of their implication in the muscle contraction fatigue that often occurs in the thymomaassociated MG and reflects a defect in the physiological association of TRPC3 with the ryanodine receptor-1 in the excitation-contraction coupling in which the sarcoplasmic Ca2+ release takes place. In addition to the modulating role in the NMJ functions, the mAChRs participate in the innate and adaptive inmmunity by MG thymus and in the lung cancer (often associated with LEMS) growth. Synaptic Compensatory Mechanism and its Impairment in Autoimmune Myasthenic Diseases
{"title":"Synaptic Compensatory Mechanism and its Impairment in Autoimmune Myasthenic Diseases","authors":"M. Takamori","doi":"10.29245/2578-3009/2019/3.1173","DOIUrl":"https://doi.org/10.29245/2578-3009/2019/3.1173","url":null,"abstract":"The neuromuscular junction (NMJ) is organized by a complex architecture and various signals orchestrated by sophisticated interactions. They include the presynaptic Ca2+ homeostasis for acetylcholine (ACh) release in the active zone organization, the post-synaptic ACh receptor (AChR) clustering at endplate membranes, the trans-synaptic communication from muscle to nerve, and the synaptic stabilization. The present data and discussions are concerned in an adaptive change of ACh release from the nerve terminal and its immunological impairment in the post-synaptic disease (myasthenia gravis, MG) and the presynaptic disease (Lambert-Eaton myasthenic syndrome, LEMS). Discussions mainly focus the antibody-induced failure of the synaptic compensatory mechanisms that are brought about by the presynaptic autoreceptors (the M1type muscarinic AChR [mAChR] cooperated with adenosine receptors), and the non-voltage-gated Ca2+-dominant influx channel (transient receptor potential canonical [TRPCs], particularly its phenotype TRPC3). Besides the synaptic transmission fatigue, the TRPC3 antibodies are discussed in terms of their implication in the muscle contraction fatigue that often occurs in the thymomaassociated MG and reflects a defect in the physiological association of TRPC3 with the ryanodine receptor-1 in the excitation-contraction coupling in which the sarcoplasmic Ca2+ release takes place. In addition to the modulating role in the NMJ functions, the mAChRs participate in the innate and adaptive inmmunity by MG thymus and in the lung cancer (often associated with LEMS) growth. Synaptic Compensatory Mechanism and its Impairment in Autoimmune Myasthenic Diseases","PeriodicalId":73785,"journal":{"name":"Journal of immunological sciences","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86552953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-05-07DOI: 10.29245/2578-3009/2019/2.1170
Richard J White, S. Abel, S. Hasan, V. Verma, T. Ranjan, S. Karlovits, Pittsburgh, Pa
Glioblastoma (GBM) carries an abysmal prognosis. Current standard of care involves an aggressive multimodality approach including surgical resection followed by adjuvant chemoradiation. Despite this approach, overall survival remains poor and treatment approaches continue to evolve. Given the successes of immunotherapy in other disease sites, implementation in GBM management may improve outcomes. We conducted this retrospective National Cancer Database (NCDB) study to analyze treatment trends and outcomes from 2004-2015 regarding immunotherapy for GBM and queried for patients diagnosed between 2004-2015 with GBM and excluded patients treated without surgery, extracranial radiation, or chemotherapy as well as those lost to follow up. Of the 39,317 eligible patients in this study, 511 were treated with immunotherapy and 38,806 lack thereof. Median overall survival for all patients was 15 months with a 2 and 5 year survival rate of 29% and 8%, respectively. Factors positively influencing delivery of immunotherapy included younger age, higher income, facility location in a metropolitan location, greater distance to the treatment facility, treatment at an academic facility, treatment outside of the years 2007 to 2009, and Caucasian race. On propensity matched analysis, survival was 18 months and 17 months with and without immunotherapy, respectively (p=0.15). Higher comorbidity, lower income, and male gender predicted for worse survival. The results of the NCDB analysis showed an initial decrease and then increase in the use of immunotherapy in the management of GBM. Propensity-matched analyses did not show an overall survival benefit.
{"title":"National Trends in the Use of Targeted Therapy and Immunotherapy in the Up Front Management of Glioblastoma","authors":"Richard J White, S. Abel, S. Hasan, V. Verma, T. Ranjan, S. Karlovits, Pittsburgh, Pa","doi":"10.29245/2578-3009/2019/2.1170","DOIUrl":"https://doi.org/10.29245/2578-3009/2019/2.1170","url":null,"abstract":"Glioblastoma (GBM) carries an abysmal prognosis. Current standard of care involves an aggressive multimodality approach including surgical resection followed by adjuvant chemoradiation. Despite this approach, overall survival remains poor and treatment approaches continue to evolve. Given the successes of immunotherapy in other disease sites, implementation in GBM management may improve outcomes. We conducted this retrospective National Cancer Database (NCDB) study to analyze treatment trends and outcomes from 2004-2015 regarding immunotherapy for GBM and queried for patients diagnosed between 2004-2015 with GBM and excluded patients treated without surgery, extracranial radiation, or chemotherapy as well as those lost to follow up. \u0000Of the 39,317 eligible patients in this study, 511 were treated with immunotherapy and 38,806 lack thereof. Median overall survival for all patients was 15 months with a 2 and 5 year survival rate of 29% and 8%, respectively. Factors positively influencing delivery of immunotherapy included younger age, higher income, facility location in a metropolitan location, greater distance to the treatment facility, treatment at an academic facility, treatment outside of the years 2007 to 2009, and Caucasian race. On propensity matched analysis, survival was 18 months and 17 months with and without immunotherapy, respectively (p=0.15). Higher comorbidity, lower income, and male gender predicted for worse survival. \u0000The results of the NCDB analysis showed an initial decrease and then increase in the use of immunotherapy in the management of GBM. Propensity-matched analyses did not show an overall survival benefit.","PeriodicalId":73785,"journal":{"name":"Journal of immunological sciences","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79838018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-05-07DOI: 10.29245/2578-3009/2019/1.1167
Alison Taylor, Christopher E Rudd
The past few years has witnessed exciting progress in the application of “immune checkpoint inhibitors” (ICI) in the treatment of various human cancers1–3. This involves the use of antibody blockade with monoclonal antibodies (mAbs) that block receptor binding to their natural ligands. Programmed cell death-1 (PD-1) recognises PD ligand (PDL)-1 and PDL-2 on presenting cells and this sends signals that inhibit T-cell activation and effector cytotoxic responses. Through these mechanisms, PD-1 inhibits the immune system and can prevent autoimmune diseases 4. Tumor cells expressing PDL-1/PD-L2 can use this mechanism to evade immune surveillance, allowing disease progression. A therapeutic approach involves administration of mAbs that block the engagement of checkpoint molecules with their ligand. In the case of anti-PD-1, these mAbs block the binding of PD-1 on the T-cell with PDL-1/PDL-2 on the tumor cell, preventing recognition and allowing activation of the T-cell to provide an immune response against the tumor cell. Blockade also reverses T-cell exhaustion and restores T-cell functionality 5, 6. Furthermore, PD-1 expression on tumor-infiltrating CD8+ T-cells correlates with impaired function, while PDL1 expression on tumors facilitates escape4.
{"title":"Commentary: Small Molecule Inhibition of PD-1 Transcription is an Effective Alternative to Antibody Blockade in Cancer Therapy.","authors":"Alison Taylor, Christopher E Rudd","doi":"10.29245/2578-3009/2019/1.1167","DOIUrl":"https://doi.org/10.29245/2578-3009/2019/1.1167","url":null,"abstract":"The past few years has witnessed exciting progress in the application of “immune checkpoint inhibitors” (ICI) in the treatment of various human cancers1–3. This involves the use of antibody blockade with monoclonal antibodies (mAbs) that block receptor binding to their natural ligands. Programmed cell death-1 (PD-1) recognises PD ligand (PDL)-1 and PDL-2 on presenting cells and this sends signals that inhibit T-cell activation and effector cytotoxic responses. Through these mechanisms, PD-1 inhibits the immune system and can prevent autoimmune diseases 4. Tumor cells expressing PDL-1/PD-L2 can use this mechanism to evade immune surveillance, allowing disease progression. A therapeutic approach involves administration of mAbs that block the engagement of checkpoint molecules with their ligand. In the case of anti-PD-1, these mAbs block the binding of PD-1 on the T-cell with PDL-1/PDL-2 on the tumor cell, preventing recognition and allowing activation of the T-cell to provide an immune response against the tumor cell. Blockade also reverses T-cell exhaustion and restores T-cell functionality 5, 6. Furthermore, PD-1 expression on tumor-infiltrating CD8+ T-cells correlates with impaired function, while PDL1 expression on tumors facilitates escape4.","PeriodicalId":73785,"journal":{"name":"Journal of immunological sciences","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6525092/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37262320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-04-26DOI: 10.29245/2578-3009/2019/2.1171
R. Wegner, S. Abel, S. Hasan, Richard J White, G. Finley, D. Monga, A. Colonias
Immunotherapy (IMT) has revolutionized the treatment of stage IV non-small cell lung cancer (NSCLC). However, optimal timing of IMT in relation to stereotactic radiosurgery (SRS) or stereotactic body radiotherapy (SBRT) is unknown. Utilizing the National Cancer Database, we examined trends in IMT use in metastatic NSCLC patients and the potential survival implications of IMT timing in relation to SBRT/SRS. We queried the NCDB for patients with Stage IV NSCLC diagnosed between 2004-2015. Patients receiving IMT and SBRT/SRS to any site were included. Multivariate logistic regression identified predictors of IMT use. Receiver operator characteristic curve analysis determined an a priori timeframe between SBRT and IMT predictive of optimal overall survival (OS). Univariate and multivariate analyses identified factors predictive of OS. Propensity-adjusted Cox proportional hazard ratios were used to mitigate indication bias. Of 13,862 eligible patients, 371 received IMT. The majority (75%) received chemotherapy. IMT use was associated with improved median OS on univariate analysis (17 vs. 13 months, p<0.0001). Adenocarcinoma histology, chemotherapy use, and recent treatment year were associated with IMT. On multivariate propensity-adjusted Cox regression, predictors for improved OS included: younger age, lower comorbidity score, lower grade, private insurance, IMT use, and female sex. Patients treated ≥ 21 days (a priori threshold) after SBRT/SRS initiation had improved median OS (19 vs. 15 months, p=0.0335). In patients with Stage IV NSCLC, IMT use following SBRT/SRS has increased. OS improved when IMT was given ≥3 weeks after initiating SBRT/SRS; suggesting a potential optimal time-frame between RT and IMT.
{"title":"Time from Stereotactic Radiotherapy to Immunotherapy Is a Predictor for Outcome in Stage IV Non-Small Cell Lung Cancer","authors":"R. Wegner, S. Abel, S. Hasan, Richard J White, G. Finley, D. Monga, A. Colonias","doi":"10.29245/2578-3009/2019/2.1171","DOIUrl":"https://doi.org/10.29245/2578-3009/2019/2.1171","url":null,"abstract":"Immunotherapy (IMT) has revolutionized the treatment of stage IV non-small cell lung cancer (NSCLC). However, optimal timing of IMT in relation to stereotactic radiosurgery (SRS) or stereotactic body radiotherapy (SBRT) is unknown. Utilizing the National Cancer Database, we examined trends in IMT use in metastatic NSCLC patients and the potential survival implications of IMT timing in relation to SBRT/SRS. We queried the NCDB for patients with Stage IV NSCLC diagnosed between 2004-2015. Patients receiving IMT and SBRT/SRS to any site were included. Multivariate logistic regression identified predictors of IMT use. Receiver operator characteristic curve analysis determined an a priori timeframe between SBRT and IMT predictive of optimal overall survival (OS). Univariate and multivariate analyses identified factors predictive of OS. Propensity-adjusted Cox proportional hazard ratios were used to mitigate indication bias. Of 13,862 eligible patients, 371 received IMT. The majority (75%) received chemotherapy. IMT use was associated with improved median OS on univariate analysis (17 vs. 13 months, p<0.0001). Adenocarcinoma histology, chemotherapy use, and recent treatment year were associated with IMT. On multivariate propensity-adjusted Cox regression, predictors for improved OS included: younger age, lower comorbidity score, lower grade, private insurance, IMT use, and female sex. Patients treated ≥ 21 days (a priori threshold) after SBRT/SRS initiation had improved median OS (19 vs. 15 months, p=0.0335). In patients with Stage IV NSCLC, IMT use following SBRT/SRS has increased. OS improved when IMT was given ≥3 weeks after initiating SBRT/SRS; suggesting a potential optimal time-frame between RT and IMT.","PeriodicalId":73785,"journal":{"name":"Journal of immunological sciences","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86006504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-04-26DOI: 10.29245/2578-3009/2019/2.1168
G. Kirchenbaum, Jodi Hanson, D. Roen, Paul Lehmann
T cells not only protect us from infectious diseases and cancer, but are also involved in transplant rejection, autoimmune diseases, and allergies. Each of these immunologic processes share a common link in which antigen-specific T cells undergo expansion, with some of the resulting progeny differentiating into memory cells. Memory T cells belong to several distinct lineages, and sub-lineages, that fundamentally differ in their effector functions and capacity to mediate a protective or pathological immune response. In this mini-review, we outline how such memory T cell subpopulations can readily be identified on the basis of their secretory signature using a multi-color ImmunoSpot® assay.
{"title":"Detection of Antigen-Specific T Cell Lineages and Effector Functions Based on Secretory Signature","authors":"G. Kirchenbaum, Jodi Hanson, D. Roen, Paul Lehmann","doi":"10.29245/2578-3009/2019/2.1168","DOIUrl":"https://doi.org/10.29245/2578-3009/2019/2.1168","url":null,"abstract":"T cells not only protect us from infectious diseases and cancer, but are also involved in transplant rejection, autoimmune diseases, and allergies. Each of these immunologic processes share a common link in which antigen-specific T cells undergo expansion, with some of the resulting progeny differentiating into memory cells. Memory T cells belong to several distinct lineages, and sub-lineages, that fundamentally differ in their effector functions and capacity to mediate a protective or pathological immune response. In this mini-review, we outline how such memory T cell subpopulations can readily be identified on the basis of their secretory signature using a multi-color ImmunoSpot® assay.","PeriodicalId":73785,"journal":{"name":"Journal of immunological sciences","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83405060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-01-01DOI: 10.29245/2578-3009/2019/1.1150
C. S. Simoneti, E. Vianna
{"title":"Commentary: Exposure to High Endotoxin Concentration Increases Wheezing Prevalence Among Laboratory Animal Workers: A Cross-Sectional Study","authors":"C. S. Simoneti, E. Vianna","doi":"10.29245/2578-3009/2019/1.1150","DOIUrl":"https://doi.org/10.29245/2578-3009/2019/1.1150","url":null,"abstract":"","PeriodicalId":73785,"journal":{"name":"Journal of immunological sciences","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87012700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-01-01Epub Date: 2019-01-10DOI: 10.29245/2578-3009/2019/1.1165
Kaity H Tung, Marc S Ernstoff, Cheryl Allen, Shin La Shu
Tumor-derived exosomes (TEX) are important intercellular messengers that contribute to tumorigenesis and metastasis through a variety of mechanisms such as immunosuppression and metabolic reprogramming that generate a pre-metastatic niche favorable to tumor progression. Our lab has contributed further to the understanding of the miRNA payloads in TEX by demonstrating that human melanoma-derived exosome (HMEX) associated miRNAs contribute to the metabolic reprogramming of normal stroma. This mini-review highlights the role of TEX in the tumor microenvironment (TME) and the hypothesis that exosomes may also generate a host-tumor "macroenvironment" beyond the TME through their miRNA and protein payloads, so to speak "fertilizing the soil for cancer seeding."
{"title":"A Review of Exosomes and their Role in The Tumor Microenvironment and Host-Tumor \"Macroenvironment\".","authors":"Kaity H Tung, Marc S Ernstoff, Cheryl Allen, Shin La Shu","doi":"10.29245/2578-3009/2019/1.1165","DOIUrl":"https://doi.org/10.29245/2578-3009/2019/1.1165","url":null,"abstract":"<p><p>Tumor-derived exosomes (TEX) are important intercellular messengers that contribute to tumorigenesis and metastasis through a variety of mechanisms such as immunosuppression and metabolic reprogramming that generate a pre-metastatic niche favorable to tumor progression. Our lab has contributed further to the understanding of the miRNA payloads in TEX by demonstrating that human melanoma-derived exosome (HMEX) associated miRNAs contribute to the metabolic reprogramming of normal stroma. This mini-review highlights the role of TEX in the tumor microenvironment (TME) and the hypothesis that exosomes may also generate a host-tumor \"macroenvironment\" beyond the TME through their miRNA and protein payloads, so to speak \"fertilizing the soil for cancer seeding.\"</p>","PeriodicalId":73785,"journal":{"name":"Journal of immunological sciences","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.29245/2578-3009/2019/1.1165","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37142092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-01-01Epub Date: 2019-03-19DOI: 10.29245/2578-3009/2019/2.1166
Hildegard M Schuller
This mini-review summarizes current knowledge on similarities and synergism between smoking and psychological stress-induced modulations of growth stimulating and inhibiting regulatory networks in epithelial cells and epithelial cancers with emphasis on cancer stimulating neurotransmitters and their receptors as well as cancer inhibiting γ-aminobutyric acid (GABA) and opioids. Hyperactive cAMP signaling downstream of beta-adrenergic receptors (β-ARs) has been identified as the driving force of most smoking-associated cancers by numerous preclinical studies and psychological stress intensifies these effects while experimental stress reduction inhibits. The integration of cAMP reduction via stress reduction by pharmacological and psychological means such as psychotherapy, relaxation meditation and yoga into any cancer treatment strategy is recommended.
{"title":"The Neuro-Psychological Axis of Smoking-Associated Cancer.","authors":"Hildegard M Schuller","doi":"10.29245/2578-3009/2019/2.1166","DOIUrl":"https://doi.org/10.29245/2578-3009/2019/2.1166","url":null,"abstract":"<p><p>This mini-review summarizes current knowledge on similarities and synergism between smoking and psychological stress-induced modulations of growth stimulating and inhibiting regulatory networks in epithelial cells and epithelial cancers with emphasis on cancer stimulating neurotransmitters and their receptors as well as cancer inhibiting γ-aminobutyric acid (GABA) and opioids. Hyperactive cAMP signaling downstream of beta-adrenergic receptors (β-ARs) has been identified as the driving force of most smoking-associated cancers by numerous preclinical studies and psychological stress intensifies these effects while experimental stress reduction inhibits. The integration of cAMP reduction via stress reduction by pharmacological and psychological means such as psychotherapy, relaxation meditation and yoga into any cancer treatment strategy is recommended.</p>","PeriodicalId":73785,"journal":{"name":"Journal of immunological sciences","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6594710/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37367425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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