Immunological Correlates of Response to Immune Checkpoint Inhibitors in Metastatic Urothelial Carcinoma.


BACKGROUND:The identification of prognostic and/or predictive biomarkers for response to immune checkpoint inhibitors (ICI) could help guide treatment decisions. OBJECTIVE:We assessed changes in programmed cell death-1 (PD1)/PD1 ligand (PDL1) expression in key immunomodulatory cell subsets (myeloid-derived suppressor cells [MDSC]; cytotoxic T lymphocytes [CTL]) following ICI therapy and investigated whether these changes correlated with outcomes in patients with metastatic urothelial carcinoma (mUC). PATIENTS AND METHODS:Serial peripheral blood samples were collected from ICI-treated mUC patients. Flow cytometry was used to quantify PD1/PDL1 expression on MDSC (CD33+HLADR-) and CTL (CD8+CD4-) from peripheral blood mononuclear cells. MDSC were grouped into monocytic (M)-MDSC (CD14+CD15-), polymorphonuclear (PMN)-MDSC (CD14-CD15+), and immature (I)-MDSC (CD14-CD15-). Mixed-model regression and Wilcoxon signed-rank or rank-sum tests were performed to assess post-ICI changes in immune biomarker expression and identify correlations between PD1/PDL1 expression and objective response to ICI. RESULTS:Of 41 ICI-treated patients, 26 received anti-PDL1 (23 atezolizumab/3 avelumab) and 15 received anti-PD1 (pembrolizumab) therapy. Based on available data, 27.5% had prior intravesical Bacillus Calmette-Guérin therapy, 42% had prior neoadjuvant chemotherapy, and 70% had prior cystectomy or nephroureterectomy. Successive doses of anti-PDL1 correlated with decreased percentage of PDL1+ (%PDL1+) M-MDSC, while doses of anti-PD1 correlated with decreased %PD1+ M- and I-MDSC. Although pre-treatment %PD1+ CTL did not predict response, a greater %PD1+ CTL within 9 weeks after ICI initiation correlated with objective response. CONCLUSIONS:Treatment with ICI correlated with distinct changes in PD1/PDL1-expressing peripheral immune cell subsets, which may predict objective response to ICI. Further studies are required to validate immune molecular expression as a prognostic and/or predictive biomarker for long-term outcomes in mUC.


Target Oncol


Targeted oncology


Tzeng A,Diaz-Montero CM,Rayman PA,Kim JS,Pavicic PG Jr,Finke JH,Barata PC,Lamenza M,Devonshire S,Schach K,Emamekhoo H,Ernstoff MS,Hoimes CJ,Rini BI,Garcia JA,Gilligan TD,Ornstein MC,Grivas P




Has Abstract


2018-10-01 00:00:00














  • Modulating Tumor Immunology by Inhibiting Indoleamine 2,3-Dioxygenase (IDO): Recent Developments and First Clinical Experiences.

    abstract::Indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO) catalyze the first rate-limiting step in the oxidative metabolism of compounds containing indole rings, including the transformation of the essential amino acid L-tryptophan to N-formyl-L-kynurenine. Through direct and indirect means, IDO exerts bo...

    journal_title:Targeted oncology

    pub_type: 杂志文章,评审


    authors: Davar D,Bahary N

    更新日期:2018-04-01 00:00:00

  • Therapeutically targeting the SUMOylation, Ubiquitination and Proteasome pathways as a novel anticancer strategy.

    abstract::The ubiquitin (Ub)+proteasome proteolytic pathway is responsible for the selective degradation of the majority of nuclear and cytosolic proteins. The proteasome is a high molecular weight multicatalytic protease that serves as the catalytic core of the complex Ub-dependent protein degradation pathway and is an excitin...

    journal_title:Targeted oncology

    pub_type: 杂志文章,评审


    authors: Driscoll JJ,Dechowdhury R

    更新日期:2010-12-01 00:00:00

  • Activity and safety of erlotinib as second- and third-line treatment in elderly patients with advanced non-small cell lung cancer: a phase II trial.

    abstract::Erlotinib is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor. Efficacy of this drug was documented in the BR.21 trial showing that adenocarcinoma, female gender, Asian ethnicity and never-smoker status are predictive of clinical response to erlotinib. Retrospective studies documented the same bene...

    journal_title:Targeted oncology

    pub_type: 杂志文章


    authors: Rossi D,Dennetta D,Ugolini M,Catalano V,Alessandroni P,Giordani P,Baldelli AM,Casadei V,Graziano F,Luzi Fedeli S

    更新日期:2010-12-01 00:00:00

  • QTc prolongation induced by targeted biotherapies used in clinical practice and under investigation: a comprehensive review.

    abstract::In anticancer drug development, there has been increasing consideration for the potential of a compound to cause adverse electrocardiographic changes, especially QT interval prolongation, which can be associated with risk of torsades de pointes and sudden death. Irrespective of overt clinical toxicities, QTc assessmen...

    journal_title:Targeted oncology

    pub_type: 杂志文章,评审


    authors: Locatelli M,Criscitiello C,Esposito A,Minchella I,Goldhirsch A,Cipolla C,Curigliano G

    更新日期:2015-03-01 00:00:00

  • Clinical activity of sunitinib in patients with advanced desmoplastic round cell tumor: a case series.

    abstract::Desmoplastic small round cell tumor (DSRCT) is a rare and aggressive malignancy with poor outcome occurring in adolescents and young adults. Therapeutic options for patients with advanced disease are limited. Preclinical studies have shown that VEGFR-2 and VEGFA are overexpressed in DSRCT and that DSRCT xenografts wer...

    journal_title:Targeted oncology

    pub_type: 杂志文章


    authors: Italiano A,Kind M,Cioffi A,Maki RG,Bui B

    更新日期:2013-09-01 00:00:00

  • Tumours and tissues: similar homeostatic systems?

    abstract::The currently prevalent somatic mutation theory of carcinogenesis and metastases explicitly assumes that cancer is a cellular disease, i.e. a disease of the control of cell proliferation and/or cell differentiation. Accordingly, explanations should always be sought for at a gene and/or gene product level, regardless o...

    journal_title:Targeted oncology

    pub_type: 杂志文章,评审


    authors: Demicheli R

    更新日期:2013-06-01 00:00:00

  • Posterior reversible encephalopathy syndrome induced by anti-VEGF agents.

    abstract::Posterior reversible encephalopathy syndrome (PRES) is a clinico-radiological entity that may occur in patients receiving anti-vascular endothelial growth factor (VEGF) agents such as bevacizumab and tyrosine kinase inhibitors. Little is known about the characteristics of patients at risk for PRES under anti-VEGF agen...

    journal_title:Targeted oncology

    pub_type: 杂志文章,meta分析,评审


    authors: Tlemsani C,Mir O,Boudou-Rouquette P,Huillard O,Maley K,Ropert S,Coriat R,Goldwasser F

    更新日期:2011-12-01 00:00:00

  • Atezolizumab First-Line Combination Therapy: A Review in Metastatic Nonsquamous NSCLC.

    abstract::Atezolizumab (Tecentriq®), a humanized, anti-programmed cell death ligand-1 (PD-L1) monoclonal antibody, in combination with bevacizumab, carboplatin and paclitaxel (ABCP) or with carboplatin and nab-paclitaxel (ACnP) has been approved as first-line treatment for metastatic nonsquamous NSCLC, based on results from the...

    journal_title:Targeted oncology

    pub_type: 杂志文章,评审


    authors: Dhillon S,Syed YY

    更新日期:2019-12-01 00:00:00

  • Prognostic significance of host immune status in patients with late relapsing renal cell carcinoma treated with targeted therapy.

    abstract::We aimed to assess the prognostic role of pretreatment neutrophilia, lymphocytopenia, and neutrophil to lymphocyte ratio (NLR) in patients treated with vascular endothelial growth factor-tyrosine kinase inhibitors (VEGFR-TKIs) for late relapsing (>5 years) metastatic renal cell carcinoma (mRCC). Data were collected fr...

    journal_title:Targeted oncology

    pub_type: 杂志文章


    authors: Santoni M,Buti S,Conti A,Porta C,Procopio G,Sternberg CN,Bracarda S,Basso U,De Giorgi U,Rizzo M,Derosa L,Ortega C,Massari F,Milella M,Bersanelli M,Cerbone L,Muzzonigro G,Burattini L,Montironi R,Santini D,Cascinu S

    更新日期:2015-12-01 00:00:00

  • Cardiovascular toxicities: clues to optimal administration of vascular endothelial growth factor signaling pathway inhibitors.

    abstract::Several angiogenesis inhibitors have been approved for commercial use and many additional agents are under development for the treatment of various malignancies. Cardiovascular toxicities have been increasingly recognized as effects of this entire class of new anticancer therapeutics. There is a limited but growing un...

    journal_title:Targeted oncology

    pub_type: 杂志文章,评审


    authors: Snider KL,Maitland ML

    更新日期:2009-04-01 00:00:00

  • Targeted therapies in thyroid cancer.

    abstract::Differentiated thyroid carcinoma is the most frequent neoplasm of the endocrine system. Although thyroid cancer usually has an excellent prognosis, no therapeutic options are available for patients that develop metastases and are or became resistant to radioiodine therapy. The deeper knowledge of molecular aberrations...

    journal_title:Targeted oncology

    pub_type: 杂志文章


    authors: Capdevila J,Perez-Garcia J,Obiols G,Tabernero J

    更新日期:2009-12-01 00:00:00

  • Renal Toxicities of Targeted Therapies.

    abstract::With the incorporation of targeted therapies in routine cancer therapy, it is imperative that the array of toxicities associated with these agents be well-recognized and managed, especially since these toxicities are distinct from those seen with conventional cytotoxic agents. This review will focus on these renal tox...

    journal_title:Targeted oncology

    pub_type: 杂志文章,评审


    authors: Abbas A,Mirza MM,Ganti AK,Tendulkar K

    更新日期:2015-12-01 00:00:00

  • Inflammatory Indexes as Prognostic and Predictive Factors in Ovarian Cancer Treated with Chemotherapy Alone or Together with Bevacizumab. A Multicenter, Retrospective Analysis by the MITO Group (MITO 24).

    abstract:BACKGROUND:The variability in progression-free survival (PFS) and overall survival (OS) among patients with epithelial ovarian cancer (EOC) makes it difficult to reliably predict outcomes. A predictive biomarker of bevacizumab efficacy as first-line therapy in EOC is still lacking. OBJECTIVE:The MITO group conducted a...

    journal_title:Targeted oncology

    pub_type: 杂志文章,多中心研究


    authors: Farolfi A,Petrone M,Scarpi E,Gallà V,Greco F,Casanova C,Longo L,Cormio G,Orditura M,Bologna A,Zavallone L,Ventriglia J,Franzese E,Loizzi V,Giardina D,Pigozzi E,Cioffi R,Pignata S,Giorda G,De Giorgi U

    更新日期:2018-08-01 00:00:00

  • Vitamin D Deficiency has a Negative Impact on Cetuximab-Mediated Cellular Cytotoxicity against Human Colon Carcinoma Cells.

    abstract:BACKGROUND:Hypovitaminosis D is associated with an adverse prognosis in colon cancer patients, possibly due to the effects of the vitamin on the immune system. Antibody-dependent cell-mediated cytotoxicity (ADCC) significantly contributes to the anti-tumor effects of monoclonal antibodies, including cetuximab, an epide...

    journal_title:Targeted oncology

    pub_type: 杂志文章


    authors: Mortara L,Gariboldi MB,Bosi A,Bregni M,Pinotti G,Guasti L,Squizzato A,Noonan DM,Monti E,Campiotti L

    更新日期:2018-10-01 00:00:00

  • Imaging response in neuroendocrine tumors treated with targeted therapies: the experience of sunitinib.

    abstract::Among neuroendocrine carcinomas of the gut, well-differentiated tumors are highly vascularized, featuring specific characteristics on contrast-enhanced imaging. Well-differentiated neuroendocrine tumors spontaneously harbor hypervascular enhancement, coexisting with areas of necrosis mainly located at the center of tu...

    journal_title:Targeted oncology

    pub_type: 杂志文章


    authors: Faivre S,Ronot M,Dreyer C,Serrate C,Hentic O,Bouattour M,Bruno O,Couvelard A,Vilgrain V,Raymond E

    更新日期:2012-06-01 00:00:00

  • The Role of Mesothelin as a Diagnostic and Therapeutic Target in Pancreatic Ductal Adenocarcinoma: A Comprehensive Review.

    abstract::Mesothelin is a tumor differentiation antigen, which is highly expressed in several solid neoplasms, including pancreatic cancer. Its selective expression on malignant cells and on only a limited number of healthy tissues has made it an interesting candidate for investigation as a diagnostic and prognostic biomarker a...

    journal_title:Targeted oncology

    pub_type: 杂志文章,评审


    authors: Nichetti F,Marra A,Corti F,Guidi A,Raimondi A,Prinzi N,de Braud F,Pusceddu S

    更新日期:2018-06-01 00:00:00

  • Weekly and every 2 weeks cetuximab maintenance therapy after platinum-based chemotherapy plus cetuximab as first-line treatment for non-small cell lung cancer: randomized non-comparative phase IIIb NEXT trial.

    abstract::The First-Line Erbitux in Lung Cancer (FLEX) trial showed that the addition of cetuximab to chemotherapy followed by weekly cetuximab maintenance significantly improved survival in the first-line treatment of advanced non-small cell lung cancer (NSCLC). The phase IIIb NSCLC Erbitux Trial (NEXT) trial (NCT00820755) inv...

    journal_title:Targeted oncology

    pub_type: 杂志文章,多中心研究,随机对照试验


    authors: Heigener DF,Pereira JR,Felip E,Mazal J,Manzyuk L,Tan EH,Merimsky O,Sarholz B,Esser R,Gatzemeier U

    更新日期:2015-06-01 00:00:00

  • Acquired Resistance to Erlotinib in EGFR Mutation-Positive Lung Adenocarcinoma among Hispanics (CLICaP).

    abstract:BACKGROUND:Lung cancer harboring epidermal growth factor receptor (EGFR) mutations and treated with EGFR tyrosine kinase inhibitors (TKIs) all eventually develop acquired resistance to the treatment, with half of the patients developing EGFR T790M resistance mutations. OBJECTIVE:The purpose of this study was to assess...

    journal_title:Targeted oncology

    pub_type: 杂志文章


    authors: Cardona AF,Arrieta O,Zapata MI,Rojas L,Wills B,Reguart N,Karachaliou N,Carranza H,Vargas C,Otero J,Archila P,Martín C,Corrales L,Cuello M,Ortiz C,Pino LE,Rosell R,Zatarain-Barrón ZL,CLICaP.

    更新日期:2017-08-01 00:00:00

  • The Multifaceted Roles of B Cells in Solid Tumors: Emerging Treatment Opportunities.

    abstract::The influence of tumor infiltrating lymphocytes on tumor growth and response to therapy is becoming increasingly apparent. While much work has focused on the role of T cell responses in anti-tumor immunity, the role of B cells in solid tumors is much less understood. Tumor infiltrating B cells have been found in a var...

    journal_title:Targeted oncology

    pub_type: 杂志文章,评审


    authors: Flynn NJ,Somasundaram R,Arnold KM,Sims-Mourtada J

    更新日期:2017-04-01 00:00:00

  • Identification of driver mutations in lung cancer: first step in personalized cancer.

    abstract::Non-small cell lung cancer (NSCLC) has recently been associated with interesting molecular characteristics that have important implications in carcinogenesis and response to targeted therapies. Targeted therapies, if given to a patient subpopulation enriched by the presence of relevant molecular targets, can often abr...

    journal_title:Targeted oncology

    pub_type: 杂志文章


    authors: Planchard D

    更新日期:2013-03-01 00:00:00

  • Targeting multiple oncogenic pathways for the treatment of hepatocellular carcinoma.

    abstract::Hepatocellular carcinoma (HCC) is one of the most common forms of liver cancer diagnosed worldwide. HCC occurs due to chronic liver disease and is often diagnosed at advanced stages. Chemotherapeutic agents such as doxorubicin are currently used as first-line agents for HCC therapy, but these are non-selective cytotox...

    journal_title:Targeted oncology

    pub_type: 杂志文章,评审


    authors: Swamy SG,Kameshwar VH,Shubha PB,Looi CY,Shanmugam MK,Arfuso F,Dharmarajan A,Sethi G,Shivananju NS,Bishayee A

    更新日期:2017-02-01 00:00:00

  • Impact of biomarkers on non-small cell lung cancer treatment.

    abstract::Chemotherapy represents the mainstay of non-small cell lung cancer (NSCLC) treatment, but response is usually observed in only one out of three patients. Massive efforts have been carried out to identify biomarkers that might help clinicians to choose appropriate drugs, by identifying potentially sensitive subjects an...

    journal_title:Targeted oncology

    pub_type: 杂志文章,评审


    authors: Toschi L,Cappuzzo F

    更新日期:2010-03-01 00:00:00

  • Serum Alpha1-Globulin as a Novel Prognostic Factor in Metastatic Renal Cell Carcinoma Treated with Tyrosine Kinase Inhibitors.

    abstract:BACKGROUND:Serum protein fraction (SPF) is a common parameter reflecting the nutritional and inflammatory status of the human body. However, its role in patients with cancer, particularly those treated with targeted agents, is unknown. OBJECTIVE:We conducted this study to explore the prognostic value of SPF in patient...

    journal_title:Targeted oncology

    pub_type: 杂志文章


    authors: Chen X,Yao J,Liu L,Zheng W,Hu X,Zhu Y,Wang H,Guo J

    更新日期:2019-04-01 00:00:00

  • Gastric Inflammatory Prognostic Index (GIPI) in Patients with Metastatic Gastro-Esophageal Junction/Gastric Cancer Treated with PD-1/PD-L1 Immune Checkpoint Inhibitors.

    abstract:BACKGROUND:Immune checkpoint inhibitors (ICIs) demonstrated improved overall survival (OS) in heavily pretreated unselected patients with metastatic gastro-esophageal junction (mGOJ)/gastric cancer (GC). Attempts to select patients based on programmed death-ligand 1 (PD-L1) expression appear to be suboptimal. A strong ...

    journal_title:Targeted oncology

    pub_type: 杂志文章


    authors: Formica V,Morelli C,Patrikidou A,Murias C,Butt S,Nardecchia A,Lucchetti J,Renzi N,Shiu KK,Roselli M,Arkenau HT

    更新日期:2020-06-01 00:00:00

  • Low Baseline Serum Sodium Concentration Is Associated with Poor Clinical Outcomes in Metastatic Non-Small Cell Lung Cancer Patients Treated with Immunotherapy.

    abstract:BACKGROUND:A consistent percentage of patients with metastatic non-small cell lung cancer (NSCLC) derives no or only marginal benefit from immunotherapy (IO). OBJECTIVE:Since serum sodium has been linked to both prognosis in NSCLC and modulation of immune cells activity, we aimed to assess the association between low ...

    journal_title:Targeted oncology

    pub_type: 杂志文章


    authors: Fucà G,Galli G,Poggi M,Lo Russo G,Proto C,Imbimbo M,Vitali M,Ganzinelli M,Lanti C,Molino G,Stangoni F,Zilembo N,de Braud F,Garassino MC,Signorelli D

    更新日期:2018-12-01 00:00:00

  • EGFR intron-1 CA repeat polymorphism is a predictor of relapse and survival in complete resected only surgically treated esophageal cancer.

    abstract::Basal transcription regulation of the epidermal growth factor receptor is dependent upon a CA simple sequence repeat polymorphism in the intron-1 (CA-SSR-1). Here, we evaluate the role of CA-SSR-1 in complete resected esophageal cancer (EC) patients without neoadjuvant or adjuvant treatment. Genomic DNA was extracted ...

    journal_title:Targeted oncology

    pub_type: 杂志文章


    authors: Vashist YK,Trump F,Gebauer F,Kutup A,Güngör C,Kalinin V,Muddasar R,Vettorazzi E,Yekebas EF,Brandt B,Pantel K,Izbicki JR

    更新日期:2014-03-01 00:00:00

  • Management of Adverse Events During Rucaparib Treatment for Relapsed Ovarian Cancer: A Review of Published Studies and Practical Guidance.

    abstract::The poly(ADP-ribose) polymerase inhibitor rucaparib is approved as monotherapy in the treatment and maintenance settings for women with relapsed ovarian cancer in the European Union and the United States. We review the safety profile of rucaparib in both settings and provide recommendations for the clinical management...

    journal_title:Targeted oncology

    pub_type: 杂志文章


    authors: Lorusso D,García-Donas J,Sehouli J,Joly F

    更新日期:2020-06-01 00:00:00

  • Delta-catenin promotes the proliferation and invasion of colorectal cancer cells by binding to E-cadherin in a competitive manner with p120 catenin.

    abstract::δ-Catenin is the only member of the p120 catenin (p120ctn) subfamily whose normal pattern of expression is restricted to the brain. Similar to p120ctn, δ-catenin can bind to the juxtamembrane domain of E-cadherin. We examined the expression of δ-catenin, p120ctn, and E-cadherin using immunohistochemistry in 95 cases o...

    journal_title:Targeted oncology

    pub_type: 杂志文章


    authors: Zhang H,Dai SD,Zhang D,Liu D,Zhang FY,Zheng TY,Cui MM,Dai CL

    更新日期:2014-03-01 00:00:00

  • Epidermal growth factor receptor tyrosine kinase inhibitors in elderly or poor performance status patients with advanced non-small cell lung cancer.

    abstract::Elderly and poor performance status advanced non-small cell lung cancer (NSCLC) patients often tolerate chemotherapy poorly. Special approaches are needed for these patient populations. Tyrosine kinase inhibitors (TKIs) of the epidermal growth factor receptor (EGFR), erlotinib and gefitinib, are active agents in the t...

    journal_title:Targeted oncology

    pub_type: 杂志文章,评审


    authors: Lin CC,Yang CH

    更新日期:2009-01-01 00:00:00

  • Sorafenib: A Review in Hepatocellular Carcinoma.

    abstract::Sorafenib (Nexavar®) is currently the only systemic agent approved for use in hepatocellular carcinoma (HCC). Its approval was based on the results of the pivotal SHARP and Sorafenib Asia-Pacific (AP) trials in Child-Pugh (CP) class A patients with advanced HCC, which showed significantly longer median overall surviva...

    journal_title:Targeted oncology

    pub_type: 杂志文章,评审


    authors: Keating GM

    更新日期:2017-04-01 00:00:00