Correlation between previous treatment with BRAF inhibitors and clinical response to pembrolizumab in patients with advanced melanoma.

Abstract:

:The optimal sequencing of targeted treatment and immunotherapy in the treatment of advanced melanoma is a key question and prospective studies to address this are ongoing. Previous observations suggest that treating first with targeted therapy may select for more aggressive disease, meaning that patients may not gain full benefit from subsequent immunotherapy. In a single-center retrospective analysis, we investigated whether response to pembrolizumab was affected by previous BRAF inhibitor therapy. A total of 42 patients with metastatic cutaneous or mucosal melanoma who had received previous treatment with ipilimumab were treated with pembrolizumab as part of the Italian expanded access program. Sixteen of these patients had BRAF-mutated melanoma and had also been previously treated with a BRAF inhibitor (vemurafenib or dabrafenib), while 26 had BRAF wild-type melanoma (no previous BRAF inhibitor). Patients with BRAF-mutant melanoma who were previously treated with BRAF inhibitors had a significantly lower median progression-free survival (3 [2.3-3.7] versus not reached [2-8+] mo; p = 0.001) and disease control rate (18.6% versus 65.4%; p = 0.005) than patients with BRAF wild-type, while there was also a trend toward a lower response rate (assessed using immune-related response criteria) although this was not significantly different between groups (12.5% versus 36.4%; p = 0.16). These data are consistent with previous reports that BRAF inhibitor therapy may affect subsequent response to immunotherapy.

journal_name

Oncoimmunology

journal_title

Oncoimmunology

authors

Simeone E,Grimaldi AM,Festino L,Giannarelli D,Vanella V,Palla M,Curvietto M,Esposito A,Palmieri G,Mozzillo N,Ascierto PA

doi

10.1080/2162402X.2017.1283462

subject

Has Abstract

pub_date

2017-01-19 00:00:00

pages

e1283462

issue

3

eissn

2162-4011

issn

2162-402X

pii

1283462

journal_volume

6

pub_type

杂志文章
  • A novel in situ multiplex immunofluorescence panel for the assessment of tumor immunopathology and response to virotherapy in pediatric glioblastoma reveals a role for checkpoint protein inhibition.

    abstract::Immunotherapy with oncolytic herpes simplex virus-1 therapy offers an innovative, targeted, less-toxic approach for treating brain tumors. However, a major obstacle in maximizing oncolytic virotherapy is a lack of comprehensive understanding of the underlying mechanisms that unfold in CNS tumors/associated microenviro...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2019.1678921

    authors: Bernstock JD,Vicario N,Rong L,Valdes PA,Choi BD,Chen JA,DiToro D,Osorio DS,Kachurak K,Gessler F,Johnston JM Jr,Atkinson TP,Whitley RJ,Bag AK,Gillespie GY,Markert JM,Maric D,Friedman GK

    更新日期:2019-10-21 00:00:00

  • Cross-priming for antitumor CTL induced by soluble Ag + polyI:C depends on the TICAM-1 pathway in mouse CD11c(+)/CD8α(+) dendritic cells.

    abstract::PolyI:C is a nucleotide pattern molecule that induces cross-presentation of foreign Ag in myeloid dendritic cells (DC) and MHC Class I-dependent proliferation of cytotoxic T lymphocytes (CTL). DC (BM or spleen CD8α(+)) have sensors for dsRNA including polyI:C to signal facilitating cross-presentation. Endosomal TLR3 a...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.4161/onci.19893

    authors: Azuma M,Ebihara T,Oshiumi H,Matsumoto M,Seya T

    更新日期:2012-08-01 00:00:00

  • A phase 1 trial extension to assess immunologic efficacy and safety of prime-boost vaccination with VXM01, an oral T cell vaccine against VEGFR2, in patients with advanced pancreatic cancer.

    abstract::VXM01 is a first-in-kind orally applied tumor vaccine based on live attenuated Salmonella typhi carrying an expression plasmid encoding VEGFR2, an antigen expressed on tumor vasculature and a stable and accessible target for anti-angiogenic intervention. A recent randomized, placebo-controlled, phase I dose-escalation...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2017.1303584

    authors: Schmitz-Winnenthal FH,Hohmann N,Schmidt T,Podola L,Friedrich T,Lubenau H,Springer M,Wieckowski S,Breiner KM,Mikus G,Büchler MW,Keller AV,Koc R,Springfeld C,Knebel P,Bucur M,Grenacher L,Haefeli WE,Beckhove P

    更新日期:2018-01-16 00:00:00

  • Chronic activation of DNA damage signals causes tumor immune evasion in the chemoresistant niche.

    abstract::DNA damage responses have been proposed as a gatekeeper to block tumorigenesis. We identify unexpected mechanisms whereby ATM-mediated pathway interacts with NFκB inflammatory cascades, leading to upregulation of integrin-αbβ3 on chemoresistant tumor cells. The integrin-αbβ3 is responsible for impeding tumor-specific ...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.4161/onci.19123

    authors: Jinushi M

    更新日期:2012-05-01 00:00:00

  • Immune cells in pancreatic cancer: Joining the dark side.

    abstract::Pancreatic tumors are rich in immune cell infiltrates that include CD4+ T-cell subsets encompassing both regulatory T cells and TH17 cells. Rather than protecting the organism by exerting an anticancer effect, these T-cell subsets promote tumor formation. Thus, re-activation of antitumor immunity should be investigate...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.4161/onci.29125

    authors: Zhang Y,McAllister F,Pasca di Magliano M

    更新日期:2014-06-05 00:00:00

  • Recent advances and new opportunities for targeting human dendritic cells in situ.

    abstract::Targeting antigens directly to dendritic cells (DCs) in situ has emerged as a promising strategy to potentiate immunity. A recent clinical trial of antibody-mediated targeting of tumor antigen NY-ESO1 to the DC receptor DEC-205 demonstrated an induction of strong cellular and humoral responses. Recent studies with DC-...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.4161/21624011.2014.954832

    authors: Dhodapkar MV,Dhodapkar KM

    更新日期:2014-08-03 00:00:00

  • Overcoming immunosuppression to enhance a p53MVA vaccine.

    abstract::A Phase I trial of a p53-targeting modified vaccinia Ankara (p53MVA) vaccine in patients afflicted with refractory gastrointestinal cancers demonstrated enhanced T-cell recognition of p53 following vaccination. However, this effect was transient suggesting that p53MVA requires combination with immunomodulatory agents ...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.4161/21624011.2014.958949

    authors: Hardwick N,Chung V,Cristea M,Ellenhorn JD,Diamond DJ

    更新日期:2014-12-15 00:00:00

  • Toward a rational design of combination therapy in cancer.

    abstract::By merging computational systems modeling and experimental approaches, we have uncovered treatments reprogramming pro-angiogenic monocytes present in breast tumor into immunologically potent cells capable of mediating an anti-tumor immune response. The unraveled pathways and ligands which underlie monocyte pro-angioge...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2015.1046674

    authors: Doucey MA,Xenarios I

    更新日期:2015-07-07 00:00:00

  • Interleukin-17A promotes the growth of human germinal center derived non-Hodgkin B cell lymphoma.

    abstract::Interleukin (IL)-17A belongs to IL-17 superfamily and binds the heterodimeric IL-17 receptor (R)(IL-17RA/IL-17RC). IL-17A promotes germinal center (GC) formation in mouse models of autoimmune or infectious diseases, but the role of IL-17A/IL-17AR complex in human neoplastic GC is unknown. In this study, we investigate...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2015.1030560

    authors: Ferretti E,Di Carlo E,Ognio E,Guarnotta C,Bertoni F,Corcione A,Prigione I,Fraternali-Orcioni G,Ribatti D,Ravetti JL,Ponzoni M,Tripodo C,Pistoia V

    更新日期:2015-06-19 00:00:00

  • Autophagy-dependent suppression of cancer immunogenicity and effector mechanisms of innate and adaptive immunity.

    abstract::The inspection of the mechanisms through which autophagy modulates immunogenic cell death revealed that the autophagic response of cancer cells to reactive oxygen species-dependent endoplasmic reticulum stress suppresses the exposure of calreticulin on the cell surface, the phenotypic maturation of dendritic cells (DC...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.4161/onci.26260

    authors: Garg AD,Dudek AM,Agostinis P

    更新日期:2013-10-01 00:00:00

  • Differential Regulation of T-cell mediated anti-tumor memory and cross-protection against the same tumor in lungs versus skin.

    abstract::A major advantage of immunotherapy of cancer is that effector cells induced at one site should be able to kill metastatic cancer cells in other sites or tissues. However, different tissues have unique immune components, and very little is known about whether effector T cells induced against tumors in one tissue can wo...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2018.1439305

    authors: O'Konek JJ,Ambrosino E,Bloom AC,Pasquet L,Massilamany C,Xia Z,Terabe M,Berzofsky JA

    更新日期:2018-04-09 00:00:00

  • Long-term outcomes of a phase I study of agonist CD40 antibody and CTLA-4 blockade in patients with metastatic melanoma.

    abstract::We report long-term clinical outcomes and immune responses observed from a phase 1 trial of agonist CD40 monoclonal antibody (mAb) and blocking CTLA-4 mAb in patients with metastatic melanoma. Twenty-four patients previously untreated with checkpoint blockade were enrolled. The agonistic CD40 mAb CP-870,893 and the CT...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2018.1468956

    authors: Bajor DL,Mick R,Riese MJ,Huang AC,Sullivan B,Richman LP,Torigian DA,George SM,Stelekati E,Chen F,Melenhorst JJ,Lacey SF,Xu X,Wherry EJ,Gangadhar TC,Amaravadi RK,Schuchter LM,Vonderheide RH

    更新日期:2018-08-20 00:00:00

  • PD-1 in human NK cells: evidence of cytoplasmic mRNA and protein expression.

    abstract::Under physiological conditions, PD-1/PD-L1 interactions regulate unwanted over-reactions of immune cells and contribute to maintain peripheral tolerance. However, in tumor microenvironment, this interaction may greatly compromise the immune-mediated anti-tumor activity. PD-1+ NK cells have been detected in high percen...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2018.1557030

    authors: Mariotti FR,Petrini S,Ingegnere T,Tumino N,Besi F,Scordamaglia F,Munari E,Pesce S,Marcenaro E,Moretta A,Vacca P,Moretta L

    更新日期:2018-12-25 00:00:00

  • HDAC inhibitors and their potential applications to glioblastoma therapy.

    abstract::Natural killer (NK) cells are integral components of the antitumor immune response. The downregulation of ligands for NK-cell stimulatory receptors represents a strategy whereby glioblastoma cells can evade NK-cell attacks. Histone deacetylase inhibitors can stimulate the (re)expression of these ligands, driving cytot...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.4161/onci.25219

    authors: Adamopoulou E,Naumann U

    更新日期:2013-08-01 00:00:00

  • A multicenter phase 1 study of solitomab (MT110, AMG 110), a bispecific EpCAM/CD3 T-cell engager (BiTE®) antibody construct, in patients with refractory solid tumors.

    abstract::We assessed the tolerability and antitumor activity of solitomab, a bispecific T-cell engager (BiTE®) antibody construct targeting epithelial cell adhesion molecule (EpCAM). Patients with relapsed/refractory solid tumors not amenable to standard therapy received solitomab as continuous IV infusion in a phase 1 dose-es...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2018.1450710

    authors: Kebenko M,Goebeler ME,Wolf M,Hasenburg A,Seggewiss-Bernhardt R,Ritter B,Rautenberg B,Atanackovic D,Kratzer A,Rottman JB,Friedrich M,Vieser E,Elm S,Patzak I,Wessiepe D,Stienen S,Fiedler W

    更新日期:2018-04-18 00:00:00

  • Tumor-infiltrating follicular helper T cells: The new kids on the block.

    abstract::By analyzing CD4+ lymphocytes in human breast carcinomas, we have recently uncovered the presence of follicular helper T cells in lesions exhibiting an extensive immune infiltrate. The presence of these specialized CD4+ T cells, which localize to the germinal centers of peritumoral tertiary lymphoid structures found i...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.4161/onci.26066

    authors: Gu-Trantien C,Willard-Gallo K

    更新日期:2013-10-01 00:00:00

  • PD-L1 expression in metastatic neuroblastoma as an additional mechanism for limiting immune surveillance.

    abstract::The prognosis of high-risk neuroblastoma (NB) remains poor, although immunotherapies with anti-GD2 antibodies have been reported to provide some benefit. Immunotherapies can be associated with an IFNγ storm that induces in tumor cells the "adaptive immune resistance" characterized by the de-novo expression of Programm...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2015.1064578

    authors: Dondero A,Pastorino F,Della Chiesa M,Corrias MV,Morandi F,Pistoia V,Olive D,Bellora F,Locatelli F,Castellano A,Moretta L,Moretta A,Bottino C,Castriconi R

    更新日期:2015-07-15 00:00:00

  • LAG-3 confers poor prognosis and its blockade reshapes antitumor response in head and neck squamous cell carcinoma.

    abstract::Immunotherapy with immune checkpoint molecule-specific monoclonal antibody have obtained encouraging results from preclinical studies and clinical trials, which promoted us to explore whether this kind of immunotherapy could be applicable to head and neck squamous cell carcinoma (HNSCC). Lymphocyte activation gene-3 (...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2016.1239005

    authors: Deng WW,Mao L,Yu GT,Bu LL,Ma SR,Liu B,Gutkind JS,Kulkarni AB,Zhang WF,Sun ZJ

    更新日期:2016-10-07 00:00:00

  • IL-6 augments IL-4-induced polarization of primary human macrophages through synergy of STAT3, STAT6 and BATF transcription factors.

    abstract::Macrophages in the tumor microenvironment respond to complex cytokine signals. How these responses shape the phenotype of tumor-associated macrophages (TAMs) is incompletely understood. Here we explored how cytokines of the tumor milieu, interleukin (IL)-6 and IL-4, interact to influence target gene expression in prim...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2018.1494110

    authors: Gupta S,Jain A,Syed SN,Snodgrass RG,Pflüger-Müller B,Leisegang MS,Weigert A,Brandes RP,Ebersberger I,Brüne B,Namgaladze D

    更新日期:2018-07-30 00:00:00

  • Temozolomide lymphodepletion enhances CAR abundance and correlates with antitumor efficacy against established glioblastoma.

    abstract::Adoptive transfer of T cells expressing chimeric antigen receptors (CARs) is an effective immunotherapy for B-cell malignancies but has failed in some solid tumors clinically. Intracerebral tumors may pose challenges that are even more significant. In order to devise a treatment strategy for patients with glioblastoma...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2018.1434464

    authors: Suryadevara CM,Desai R,Abel ML,Riccione KA,Batich KA,Shen SH,Chongsathidkiet P,Gedeon PC,Elsamadicy AA,Snyder DJ,Herndon JE 2nd,Healy P,Archer GE,Choi BD,Fecci PE,Sampson JH,Sanchez-Perez L

    更新日期:2018-02-21 00:00:00

  • Notch and TGFβ: Functional partners facilitating tumor progression.

    abstract::Cell signals integral to the tumor microenvironment influence cancer progression. Tumor-associated myeloid cells secrete pro-tumorigenic agents including, but not limited to, the potent cytokine transforming growth factor β (TGFβ). We have discovered a network of extrinsic signals including delta-like 4 (Dll4), Notch ...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.4161/onci.29029

    authors: Ohnuki H,Tosato G

    更新日期:2014-05-23 00:00:00

  • Acute myeloid leukemia and NK cells: two warriors confront each other.

    abstract::Acute myeloid leukemia (AML) is a heterogeneous disease whose therapies currently show elevated toxicity and a high rate of relapse. Recently, the burgeoning of new anti-tumor therapeutic strategies aimed at enhancing the immune response has pushed natural killer cells (NKs) into the spotlight. These cells are powerfu...

    journal_title:Oncoimmunology

    pub_type: 杂志文章,评审

    doi:10.1080/2162402X.2018.1539617

    authors: Baragaño Raneros A,López-Larrea C,Suárez-Álvarez B

    更新日期:2018-10-31 00:00:00

  • Procarcinogenic regulatory T cells in microbial-induced colon cancer.

    abstract::Regulatory T cell (Treg) promote IL-17-mediated colon tumorigenesis in multiple intestinal neoplasia (Min) mice colonized with enterotoxigenic Bacteroides fragilis (ETBF). Although they retain their immunosuppressive function, mucosal Treg are instrumental to initiate ETBF-triggered IL-17 colitis by limiting the avail...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2015.1118601

    authors: Geis AL,Housseau F

    更新日期:2015-12-21 00:00:00

  • Differential potency of regulatory T cell-mediated immunosuppression in kidney tumors compared to subcutaneous tumors.

    abstract::In many cancers, regulatory T cells (Treg) play a crucial role in suppressing the effector immune response thereby permitting tumor development. Indeed, in mouse models, their depletion can promote the regression of tumors of various origins, including renal cell carcinoma when located subcutaneous (SC). In the presen...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.4161/21624011.2014.963395

    authors: Devaud C,Westwood JA,Teng MW,John LB,Yong CS,Duong CP,Smyth MJ,Darcy PK,Kershaw MH

    更新日期:2014-12-21 00:00:00

  • Transforming the prostatic tumor microenvironment with oncolytic virotherapy.

    abstract::Prostate cancer (PCa) was estimated to have the second highest global incidence rate for male non-skin tumors and is the fifth most deadly in men thus mandating the need for novel treatment options. MG1-Maraba is a potent and versatile oncolytic virus capable of lethally infecting a variety of prostatic tumor cell lin...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2018.1445459

    authors: Atherton MJ,Stephenson KB,Tzelepis F,Bakhshinyan D,Nikota JK,Son HH,Jirovec A,Lefebvre C,Dvorkin-Gheva A,Ashkar AA,Wan Y,Stojdl DF,Belanger EC,Breau RH,Bell JC,Saad F,Singh SK,Diallo JS,Lichty BD

    更新日期:2018-03-27 00:00:00

  • SOX2-specific adaptive immunity and response to immunotherapy in non-small cell lung cancer.

    abstract::Immunotherapeutic strategies including the blockade of programmed death 1 (PD-1) receptors hold promise for the treatment of various cancers including non-small cell lung carcinoma (NSCLC). Preclinical data suggest that pre-existing tumor immunity is important for disease regression upon checkpoint blockade-based ther...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.4161/onci.25205

    authors: Dhodapkar KM,Gettinger SN,Das R,Zebroski H,Dhodapkar MV

    更新日期:2013-07-01 00:00:00

  • PD-L1 and epithelial-mesenchymal transition in circulating tumor cells from non-small cell lung cancer patients: A molecular shield to evade immune system?

    abstract::The programmed cell death 1 (PD-1)/PD-1 ligand 1 (PD-L1) pathway has emerged as a critical inhibitory pathway regulating T-cell response in non-small-cell lung cancer (NSCLC), and the development of PD-1/PD-L1 inhibitors has changed the landscape of NSCLC therapy. Nevertheless, the high degree of non-responders demons...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2017.1315488

    authors: Raimondi C,Carpino G,Nicolazzo C,Gradilone A,Gianni W,Gelibter A,Gaudio E,Cortesi E,Gazzaniga P

    更新日期:2017-04-20 00:00:00

  • Virotherapy-recruited PMN-MDSC infiltration of mesothelioma blocks antitumor CTL by IL-10-mediated dendritic cell suppression.

    abstract::Antitumor cytotoxic T lymphocytes (CTLs) are essential for immune surveillance, yet the blockade of eliciting such CTLs during oncolytic virotherapy remains incompletely understood. Here, we show that oncolysis of mesothelioma by modified vaccinia Tiantan (MVTT) induces damage-associated molecular patterns exposure. A...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2018.1518672

    authors: Tan Z,Liu L,Chiu MS,Cheung KW,Yan CW,Yu Z,Lee BK,Liu W,Man K,Chen Z

    更新日期:2018-10-16 00:00:00

  • CAR T-cell immunotherapy of MET-expressing malignant mesothelioma.

    abstract::Mesothelioma is an incurable cancer for which effective therapies are required. Aberrant MET expression is prevalent in mesothelioma, although targeting using small molecule-based therapeutics has proven disappointing. Chimeric antigen receptors (CARs) couple the HLA-independent binding of a cell surface target to the...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2017.1363137

    authors: Thayaparan T,Petrovic RM,Achkova DY,Zabinski T,Davies DM,Klampatsa A,Parente-Pereira AC,Whilding LM,van der Stegen SJ,Woodman N,Sheaff M,Cochran JR,Spicer JF,Maher J

    更新日期:2017-08-14 00:00:00

  • The immune molecular landscape of the B7 and TNFR immunoregulatory ligand-receptor families in head and neck cancer: A comprehensive overview and the immunotherapeutic implications.

    abstract::The B7 family and tumor necrosis factor receptor (TNFR) superfamily play a vital role in the T-cell co-stimulatory and co-inhibitory pathways, regulating T-cell activation, tolerance, and exhaustion; therapeutic modulation of these pathways is translated into effective new cancer treatments. Better understanding of th...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2017.1288329

    authors: Chen YP,Zhang J,Wang YQ,Liu N,He QM,Yang XJ,Sun Y,Ma J

    更新日期:2017-02-16 00:00:00