Lack of T-cell responses following autologous tumour lysate pulsed dendritic cell vaccination, in patients with relapsed osteosarcoma

Himoudi, Nourredine; Wallace, Rebecca; Parsley, Kathryn L.; Gilmour, Kimberly; Barrie, Alpha-Umaru; Howe, Karen; Dong, Rong; Sebire, Neil J.; Michalski, Antony; Thrasher, Adrian J.; Anderson, John

doi:10.1007/s12094-012-0795-1

Cited by 60 publications

(49 citation statements)

References 19 publications

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“…In particular, autologous DCs pulsed ex vivo with purified TAAs or TAA-derived peptides, administered as a standalone intervention or combined with chemo- or immunotherapeutic agents, have been investigated for their ability to elicit tumor-specific immune responses, and hence exert antineoplastic effects, in glioma, 234 , 235 glioblastoma, 236 , 237 multiple myeloma, 238 melanoma, 239 - 241 ductal carcinoma in situ, 242 and hepatocellular carcinoma patients 243 . Along similar lines, the safety and efficacy of autologous DCs loaded ex vivo with tumor lysates, alone or combined with other chemo- or immunotherapeutic regimens, have been tested in cohorts of patients affected by glioblastoma, 244 osteosarcoma, 245 renal cell carcinoma (RCC), 246 and other solid tumors 247 . The clinical profile of DCs engineered to express one or several TAAs (alone or together with co-stimulatory molecules such as CD40 ligand, CD70 and a constitutively active variant of TLR4) has been explored in nasopharyngeal carcinoma, 248 melanoma, 249 small cell lung cancer 250 and colorectal carcinoma (CRC) patients 251 .…”

Section: Literature Updatementioning

confidence: 99%

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et al. 2013

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Dendritic cells (DCs) occupy a privileged position at the interface between innate and adaptive immunity, orchestrating a large panel of responses to both physiological and pathological cues. In particular, whereas the presentation of antigens by immature DCs generally results in the development of immunological tolerance, mature DCs are capable of priming robust, and hence therapeutically relevant, adaptive immune responses. In line with this notion, functional defects in the DC compartment have been shown to etiologically contribute to pathological conditions including (but perhaps not limited to) infectious diseases, allergic and autoimmune disorders, graft rejection and cancer. Thus, the possibility of harnessing the elevated immunological potential of DCs for anticancer therapy has attracted considerable interest from both researchers and clinicians over the last decade. Alongside, several methods have been developed not only to isolate DCs from cancer patients, expand them, load them with tumor-associated antigens and hence generate highly immunogenic clinical grade infusion products, but also to directly target DCs in vivo. This intense experimental effort has culminated in 2010 with the approval by the US FDA of a DC-based preparation (sipuleucel-T, Provenge®) for the treatment of asymptomatic or minimally symptomatic metastatic castration-refractory prostate cancer. As an update to the latest Trial Watch dealing with this exciting field of research (October 2012), here we summarize recent advances in DC-based anticancer regimens, covering both high-impact studies that have been published during the last 13 mo and clinical trials that have been launched in the same period to assess the antineoplastic potential of this variant of cellular immunotherapy.

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Section: Literature Updatementioning

confidence: 99%

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et al. 2013

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“…It is well known that optimal activation of antigen-specific lymphocytes requires a combination of T-cell receptors (TCRs) and costimulatory signals [9]. In vivo manipulations of the T-cell costimulatory pathway are also being explored as a means to evoke immune responses for treatment of osteosarcoma [10]. In addition to the traditional B7-1 and B7-2 family members, other B7-CD28 family members have been discovered, including B7-H1 [11], B7-H2 [12], B7-H3 [13], B7-H4 [14], B7-DC [15] and B7-H6 [16].…”

Section: Introductionmentioning

confidence: 99%

B7-H3 is Overexpressed in Patients Suffering Osteosarcoma and Associated with Tumor Aggressiveness and Metastasis

et al. 2013

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B7-H3 is a member of the B7-family of co-stimulatory molecules, which has been shown to be broadly expressed in various tumor tissues, and which plays an important role in adaptive immune responses. The role of B7-H3 in osteosarcoma, however, remains unknown. In this study we used immunohistochemistry to analyze B7-H3 expression in 61 primary osteosarcoma tissues with case-matched adjacent normal tissues, and 37 osteochondroma and 20 bone fibrous dysplasia tissues. B7-H3 expression was expressed in 91.8% (56/61) of the osteosarcoma lesions, and the intensity of B7-H3 expression in osteosarcoma was significantly increased compared with adjacent normal tissues, osteochondroma and bone fibrous dysplasia tissues (p<0.001). Patients with high tumor B7-H3 levels had a significantly shorter survival time and recurrence time than patients with low tumor B7-H3 levels (p<0.001). Moreover, tumor B7-H3 expression inversely correlated with the number of tumor-infiltrating CD8+ T cells (p<0.05). In vitro, increasing expression of B7-H3 promotes osteosarcoma cell invasion, at least in part by upregulating matrix metalloproteinase-2 (MMP-2). In conclusion, our study provides the first evidence of B7-H3 expression in osteosarcoma cells as a potential mechanism controlling tumor immunity and invasive malignancy, and which is correlated with patients’ survival and metastasis.

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“…Anti-tumour activity was observed in some patients [84]. In 2012, 12 osteosarcoma patients were vaccinated with tumour lysate pulsed dendritic cells, but evidence of a clinical beneit was observed in only two of these patients [85]. These authors concluded that osteosarcoma patients may be relatively insensitive to DC-based vaccine treatments.…”

Section: Immune and Dendritic Cell Vaccinementioning

confidence: 99%

Immune Environment and Osteosarcoma

Heymann¹,

Heymann²

2017

Osteosarcoma - Biology, Behavior and Mechanisms

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Immune niche with its huge cell diversity including more speciically tumour iniltrating lymphocytes (TILs), tumour-associated macrophages (TAMs) regulate osteosarcoma (OS) microenvironment. TAMs exert diferential activities in the tumour development according to their polarisation. Indeed, in oncology, M1-polarised macrophages are considered as anti-tumour efectors, and M2-polarised macrophages are deined as protumour modulators by increasing the neoangiogenic process. TAM density is correlated with tumour cell proliferation, invasion, metastasis and poor prognosis in various epithelial and haematological cancers and in bone metastasis. Similarly, tumour iniltrating lymphocytes play a key role in tumour development by inducing a local tolerant environment favourable for the tumour growth. The present chapter will describe the main roles of the immune system in the pathogenesis of osteosarcoma and the most recent therapeutic development based on its regulation.

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Lack of T-cell responses following autologous tumour lysate pulsed dendritic cell vaccination, in patients with relapsed osteosarcoma

Cited by 60 publications

References 19 publications

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B7-H3 is Overexpressed in Patients Suffering Osteosarcoma and Associated with Tumor Aggressiveness and Metastasis

Immune Environment and Osteosarcoma

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