PD-L1 Inhibitors for the Treatment of Prostate Cancer

2020 ◽  
Vol 21 (15) ◽  
pp. 1558-1565
Author(s):  
Matteo Santoni ◽  
Francesco Massari ◽  
Liang Cheng ◽  
Alessia Cimadamore ◽  
Marina Scarpelli ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Trials ◽  
T Lymphocytes ◽  
Chronic Inflammation ◽  
Immune Cells ◽  
Response To Therapy ◽  
Complex Series

The carcinogenesis of prostate cancer (PCa) results from a complex series of events. Chronic inflammation and infections are crucial in this context. Infiltrating M2 type macrophages, as well as neutrophils and T lymphocytes, contribute to PCa development, progression and response to therapy. The preliminary findings on the efficacy of immunotherapy in patients with PCa were not encouraging. However, a series of studies investigating anti-PD-L1 agents such as Atezolizumab, Avelumab and Durvalumab used alone or in combination with other immunotherapies, chemotherapy or locoregional approaches are in course in this tumor. In this review, we illustrate the role of immune cells and PD-L1 expression during PCa carcinogenesis and progression, with a focus on ongoing clinical trials on anti-PD-L1 agents in this context.

scholarly journals Angiogenesis and Anti-Angiogenic Treatment in Prostate Cancer: Mechanisms of Action and Molecular Targets

2021 ◽  
Vol 22 (18) ◽  
pp. 9926
Author(s):  
Evangelia Ioannidou ◽  
Michele Moschetta ◽  
Sidrah Shah ◽  
Jack Steven Parker ◽  
Mehmet Akif Ozturk ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Trials ◽  
Chemotherapeutic Agents ◽  
Combination Therapies ◽  
Mechanisms Of Resistance ◽  
Marginal Benefit ◽  
Antiangiogenic Activity ◽  
Castration Resistant ◽  
Common Cancer

Prostate cancer (PC) is the most common cancer in men and the second leading cause of cancer-related death worldwide. Many therapeutic advances over the last two decades have led to an improvement in the survival of patients with metastatic PC, yet the majority of these patients still succumb to their disease. Antiagiogenic therapies have shown substantial benefits for many types of cancer but only a marginal benefit for PC. Ongoing clinical trials investigate antiangiogenic monotherapies or combination therapies. Despite the important role of angiogenesis in PC, clinical trials in refractory castration-resistant PC (CRPC) have demonstrated increased toxicity with no clinical benefit. A better understanding of the mechanism of angiogenesis may help to understand the failure of trials, possibly leading to the development of new targeted anti-angiogenic therapies in PC. These could include the identification of specific subsets of patients who might benefit from these therapeutic strategies. This paper provides a comprehensive review of the pathways involved in the angiogenesis, the chemotherapeutic agents with antiangiogenic activity, the available studies on anti-angiogenic agents and the potential mechanisms of resistance.

scholarly journals PET/CT and the Response to Immunotherapy in Lung Cancer

2020 ◽  
Vol 13 (3) ◽  
pp. 177-184 ◽  
Author(s):  
Laura Evangelista ◽  
Matteo Sepulcri ◽  
Giulia Pasello
Keyword(s):  
Lung Cancer ◽  
Clinical Trials ◽  
Cancer Patients ◽  
Fdg Pet ◽  
Response To Therapy ◽  
Prediction Of Response ◽  
Lung Cancer Patients ◽  
Pet Ct ◽  
Fdg Pet Ct

Objective: In recent years, the introduction of immune checkpoint inhibitors has significantly changed the outcome of patients affected by lung cancer and cutaneous melanoma. Although the clinical advantages, the selection of patients and the evaluation of response to immunotherapy remain unclear, the immune-related Response Evaluation Criteria in Solid Tumor (irRECIST) was proposed as an update of the RECIST criteria for the assessment of response to immunotherapy. However, morphological images cannot predict early response to therapy that represents a challenge in clinical practice. 18F-FDG PET/CT before and after immunotherapy has an indeterminate role, demonstrating ambiguous results due to inflammatory effects secondary to activation of the immune system. The aim of the present review was to analyze the role of PET/CT as a guide for immunotherapy, by analyzing the current status and future perspectives. Methods: A literature search was conducted in order to select all papers that discussed the role of PET/CT with FDG or other tracers in the evaluation or prediction of response to immunotherapy in lung cancer patients. Results: Many papers are now available. Many clinical trials have demonstrated the efficacy of immunotherapy in lung cancer patients. FDG PET/CT can be used for the prediction of response to immunotherapy, while its utility for the evaluation of response is not still clearly reported. Moreover, the standardization of FDG PET/CT interpretation is missing and different criteria, such as information, have been investigated until now. Conclusions: The utility of FDG PET/CT for patients with lung cancer undergoing immunotherapies is still preliminary and not well addressed. New agents for PET are promising, but large clinical trials are mandatory.

scholarly journals Linking inflammation and neuroendocrine differentiation: the role of macrophage migration inhibitory factor-mediated signaling in prostate cancer

2013 ◽  
Vol 20 (3) ◽  
pp. C1-C4 ◽  
Author(s):  
Rosalinda M Savoy ◽  
Paramita M Ghosh
Keyword(s):  
Prostate Cancer ◽  
Chronic Inflammation ◽  
Migration Inhibitory Factor ◽  
Macrophage Migration Inhibitory Factor ◽  
Neuroendocrine Differentiation ◽  
Inhibitory Factor ◽  
Macrophage Migration ◽  
Aggressive Prostate Cancer

A new paper by Tawadroset al. inEndocrine-Related Cancerdemonstrates a link between macrophage migration inhibitory factor and neuroendocrine differentiation in prostate cancer. This paper may have implications in explaining the effect of prostatitis and chronic inflammation on the development of aggressive prostate cancer.

scholarly journals Role of tumor-associated immune cells in prostate cancer: angel or devil?

2019 ◽  
Vol 21 (5) ◽  
pp. 433 ◽  
Author(s):  
Yin-Huai Wang ◽  
Shui-Qing Wu ◽  
Hao Su ◽  
Xiao-Kun Zhao
Keyword(s):  
Prostate Cancer ◽  
Immune Cells

Chemotherapy in metastatic hormone-naïve prostate cancer: Pooled analysis of randomized clinical trials.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 259-259 ◽  
Author(s):  
Paolo Fabbri ◽  
Lucia Stocchi ◽  
Stefania Nicoletti ◽  
Fabrizio Drudi ◽  
Emiliano Tamburini ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Clinical Trials ◽  
Confidence Interval ◽  
Preliminary Analysis ◽  
Randomized Clinical Trials ◽  
Pooled Analysis ◽  
Hazard Ratio ◽  
Androgen Blockade

259 Background: To assess the role of chemotherapy in metastatic, hormone-naïve prostate cancer, we presents the preliminary data of a pooled analysis comparing the outcome of patients with metastatic hormone-naïve prostate cancer. Methods: A pooled analysis of the outcome of randomized clinical trials approaching the role of docetaxel in metastatic hormone-naïve prostate cancer was performed using a random effect model. The final outcome of all the patients enrolled into the trials was the primary end point of our analysis. The pooled final result was reported as pooled Hazard Ratio and 95% Confidence Interval. The between-the trials heterogeneity was assessed using the I2 test. An α-error of 5% was identified as index of statistical significance. Overall survival of the entire population enrolled into the trials was the outcome of the preliminary analysis, while no subgroup analysis was performed in this preliminary phase of a multi-steps analysis. Results: Three trials (the CHAARTED, the STAMPEDE and the GETUG-AFU 15 trial) were considered eligible and included into the analysis. A pooled Hazard Ratio of 0.76 (95% Confidence Interval of 0.59-0.98, p = 0.037) was detected for overall survival, with an I2 of 67.8. The pooled datum was obtained observed the outcome of 951 patients treated with docetaxel plus androgen blockade and 1338 with androgen blockade alone. Conclusions: Although the between-the-trials heterogeneity seems to suggest caution in the final interpretation of the results, a significant reduction of the risk of death can be obtained with docetaxel in the treatment of metastatic hormone-naïve prostate cancer. Our preliminary analysis, including all the patients with metastatic hormone-naïve prostate cancer, seems to suggest a role of docetaxel in all the patients with metastatic disease; further data are probably needed to detect its role in some different subclasses of patients (patients with high burden of the disease, fit or unfit patients, elderly patients).

scholarly journals Role of Immune Cells in Patients with Hepatitis B Virus-Related Hepatocellular Carcinoma

2021 ◽  
Vol 22 (15) ◽  
pp. 8011
Author(s):  
Hyo-Jung Cho ◽  
Jae-Youn Cheong
Keyword(s):  
Hepatocellular Carcinoma ◽  
T Cells ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Chronic Inflammation ◽  
Cd8 T Cells ◽  
Immune Cells ◽  
Adaptive Immune ◽  
B Virus

Hepatocellular carcinoma (HCC) develops almost entirely in the presence of chronic inflammation. Chronic hepatitis B virus (HBV) infection with recurrent immune-mediated liver damage ultimately leads to cirrhosis and HCC. It is widely accepted that HBV infection induces the dysfunction of the innate and adaptive immune responses that engage various immune cells. Natural killer (NK) cells are associated with early antiviral and antitumor properties. On the other hand, inflammatory cells release various cytokines and chemokines that may promote HCC tumorigenesis. Moreover, immunosuppressive cells such as regulatory T cells (Treg) and myeloid-derived suppressive cells play a critical role in hepatocarcinogenesis. HBV-specific CD8+ T cells have been identified as pivotal players in antiviral responses, whilst extremely activated CD8+ T cells induce enormous inflammatory responses, and chronic inflammation can facilitate hepatocarcinogenesis. Controlling and maintaining the balance in the immune system is an important aspect in the management of HBV-related HCC. We conducted a review of the current knowledge on the immunopathogenesis of HBV-induced inflammation and the role of such immune activation in the tumorigenesis of HCC based on the recent studies on innate and adaptive immune cell dysfunction in HBV-related HCC.

Abstract 145: Epigenetic Modifications of Bone-Marrow Progenitor Cells Promote an M1 Phenotype in Peripheral Macrophages in Diabetes

2012 ◽  
Vol 32 (suppl_1) ◽  
Author(s):  
Katherine A Gallagher ◽  
Amrita Joshi ◽  
William Carson ◽  
Matthew Schaller ◽  
Peter Henke ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Progenitor Cells ◽  
Chronic Inflammation ◽  
Histone Methylation ◽  
Immune Cells ◽  
Epigenetic Changes ◽  
Facs Analysis ◽  
Bone Marrow Progenitor ◽  
M1 Phenotype

Introduction: Diabetic wounds are characterized by a chronic inflammatory state that is maintained by overexpression of pro-inflammatory cytokines generated by immune cells, namely macrophages. To understand this imbalance, it is critical of understand how changes in immune cells at the systemic level influence the peripheral immune cells. Work from our lab has shown that cytokines induce a histone post-translational “epigenetic signature” at promoter sites of specific genes. However, the role of histone modification of DNA on diabetic progenitor and differentiated immune cells and their impact on chronic inflammation in the periphery has not been studied. We hypothesized that epigenetic changes to bone marrow cells influences peripheral macrophage phenotypes. Methods: Bone marrow was harvested from 7 diet-induced obese mice (DIO) (mean glucose= 290) and 7 wildtype (WT) controls. In some of the mice, lin -/ckit+ population was isolated and flow cytometry (FACS) analysis was performed to isolate hematopoietic stem cells (HSC) and myeloid progenitor cells (MYP). HSC were defined as cells expressing sca1+/CD150+/flt3+ and MYP co-expression of sca1+/CD150+/FcgR-/CD105low. HSC and MYP were analyzed via FACS for the presence of chromatin marks. In other mice, BMD macrophages were isolated and propagated in cell culture. Macrophages were either untreated or skewed towards an M1 or M2 phenotype with IF-gamma or IL-4, respectively. Levels of protein and mRNA of M1/M2 products were analyzed. Additionally, at 6, 24 and 72 hours the macrophages were assessed for expression of chromatin remodeling marks via FACS analysis. Results: HSC had a 2 fold decrease in the expression of H3K9 histone methylation marks in the DIO mice as compared to WT. (Figure 1A) This pattern was also observed in the more differentiated MYP cells. (Fig 1B) Macrophages isolated from diabetic mice also reflected these histone changes, supporting the role of histone methylation on fully-differentiated macrophage gene expression. (Fig 1C) DIO macrophages demonstrated increased levels of TNF-alpha and CCL3, classic M1 phenotype markers. (Fig 1D) Conclusions: Epigenetic changes initiated in the bone marrow progenitor cells effect immune cells in the periphery, and may contribute to the chronic inflammation seen in diabetics. Manipulation of these histone modifications at the bone marrow level could allow for the development of therapies to prevent chronic inflammation in the periphery of diabetics.

Biomarkers for prostate cancer: prostate-specific antigen and beyond

2020 ◽  
Vol 58 (3) ◽  
pp. 326-339 ◽  
Author(s):  
Michael J. Duffy
Keyword(s):  
Prostate Cancer ◽  
Prostate Specific Antigen ◽  
Ad Hoc ◽  
Parp Inhibitor ◽  
Specific Antigen ◽  
Predictive Biomarkers ◽  
Response To Therapy ◽  
Average Risk ◽  
Free Psa

AbstractIn recent years, several new biomarkers supplementing the role of prostate-specific antigen (PSA) have become available for men with prostate cancer. Although widely used in an ad hoc manner, the role of PSA in screening asymptomatic men for prostate cancer is controversial. Several expert panels, however, have recently recommended limited PSA screening following informed consent in average-risk men, aged 55–69 years. As a screening test for prostate cancer however, PSA has limited specificity and leads to overdiagnosis which in turn results in overtreatment. To increase specificity and reduce the number of unnecessary biopsies, biomarkers such as percent free PSA, prostate health index (PHI) or the 4K score may be used, while Progensa PCA3 may be measured to reduce the number of repeat biopsies in men with a previously negative biopsy. In addition to its role in screening, PSA is also widely used in the management of patients with diagnosed prostate cancer such as in surveillance following diagnosis, monitoring response to therapy and in combination with both clinical and histological criteria in risk stratification for recurrence. For determining aggressiveness and predicting outcome, especially in low- or intermediate-risk men, tissue-based multigene tests such as Decipher, Oncotype DX (Prostate), Prolaris and ProMark, may be used. Emerging therapy predictive biomarkers include AR-V7 for predicting lack of response to specific anti-androgens (enzalutamide, abiraterone), BRAC1/2 mutations for predicting benefit from PARP inhibitor and PORTOS for predicting benefit from radiotherapy. With the increased availability of multiple biomarkers, personalised treatment for men with prostate cancer is finally on the horizon.

Analysis of the intricate relationship between chronic inflammation and cancer

2015 ◽  
Vol 468 (1) ◽  
pp. 1-15 ◽  
Author(s):  
Edna Zhi Pei Chai ◽  
Kodappully Sivaraman Siveen ◽  
Muthu K. Shanmugam ◽  
Frank Arfuso ◽  
Gautam Sethi
Keyword(s):  
Chronic Inflammation ◽  
Immune Cells ◽  
Patient Management ◽  
Critical Role ◽  
Tumour Microenvironment ◽  
Therapeutic Strategies ◽  
Exponential Rate ◽  
Hereditary Factors ◽  
Tumour Initiation

Deregulated inflammatory response plays a pivotal role in the initiation, development and progression of tumours. Potential molecular mechanism(s) that drive the establishment of an inflammatory-tumour microenvironment is not entirely understood owing to the complex cross-talk between pro-inflammatory and tumorigenic mediators such as cytokines, chemokines, oncogenes, enzymes, transcription factors and immune cells. These molecular mediators are critical linchpins between inflammation and cancer, and their activation and/or deactivation are influenced by both extrinsic (i.e. environmental and lifestyle) and intrinsic (i.e. hereditary) factors. At present, the research pertaining to inflammation-associated cancers is accumulating at an exponential rate. Interest stems from hope that new therapeutic strategies against molecular mediators can be identified to assist in cancer treatment and patient management. The present review outlines the various molecular and cellular inflammatory mediators responsible for tumour initiation, progression and development, and discusses the critical role of chronic inflammation in tumorigenesis.

scholarly journals Update on Prostate Cancer Diagnosis, Prognosis, and Prediction to Response to Therapy

Cells ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 20
Author(s):  
Rodolfo Montironi ◽  
Alessia Cimadamore ◽  
Antonio Lopez-Beltran ◽  
Liang Cheng ◽  
Marina Scarpelli
Keyword(s):  
Prostate Cancer ◽  
Cancer Diagnosis ◽  
Molecular Biomarkers ◽  
Response To Therapy ◽  
Special Issue ◽  
Prostate Cancer Diagnosis ◽  
Future Role ◽  
Wide Range ◽  
Prognosis And Prediction

The wide range of novelties reported in this Special Issue of the journal Cells on prostate cancer (PCa) diagnosis, prognosis, and prediction to response to therapy, has led us to a series of considerations related to a better understanding of the current and future role of effective molecular biomarkers in individual patients with PCa [...]

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