Antibody Responses to NY-ESO-1 in Primary Breast Cancer Identify a Subtype Target for Immunotherapy

The highly immunogenic human tumor antigen NY-ESO-1 (ESO) is a target of choice for anti-cancer immune therapy. In this study, we assessed spontaneous antibody (Ab) responses to ESO in a large cohort of patients with primary breast cancer (BC) and addressed the correlation between the presence of anti-ESO Ab, the expression of ESO in the tumors and their characteristics. We found detectable Ab responses to ESO in 1% of the patients. Tumors from patients with circulating Ab to ESO exhibited common characteristics, being mainly hormone receptor (HR)− invasive ductal carcinomas of high grade, including both HER2− and HER2+ tumors. In line with these results, we detected ESO expression in 20% of primary HR− BC, including both ESO Ab+ and Ab− patients, but not in HR+ BC. Interestingly, whereas expression levels in ESO+ BC were not significantly different between ESO Ab+ and Ab− patients, the former had, in average, significantly higher numbers of tumor-infiltrated lymph nodes, indicating that lymph node invasion may be required for the development of spontaneous anti-tumor immune responses. Thus, the presence of ESO Ab identifies a tumor subtype of HR− (HER2− or HER2+) primary BC with frequent ESO expression and, together with the assessment of antigen expression in the tumor, may be instrumental for the selection of patients for whom ESO-based immunotherapy may complement standard therapy

NY-ESO-1-Specific Circulating CD4+ T Cells in Ovarian Cancer Patients Are Prevalently TH1 Type Cells Undetectable in the CD25+FOXP3+Treg Compartment

Spontaneous CD4+ T-cell responses to the tumor-specific antigen NY-ESO-1 (ESO) are frequently found in patients with epithelial ovarian cancer (EOC). If these responses are of effector or/and Treg type, however, has remained unclear. Here, we have used functional approaches together with recently developed MHC class II/ESO tetramers to assess the frequency, phenotype and function of ESO-specific cells in circulating lymphocytes from EOC patients. We found that circulating ESO-specific CD4+ T cells in EOC patients with spontaneous immune responses to the antigen are prevalently TH1 type cells secreting IFN-γ but no IL-17 or IL-10 and are not suppressive. We detected tetramer+ cells ex vivo, at an average frequency of 1∶25000 memory cells, that is, significantly lower than in patients immunized with an ESO vaccine. ESO tetramer+ cells were mostly effector memory cells at advanced stages of differentiation and were not detected in circulating CD25+FOXP3+Treg. Thus, spontaneous CD4+ T-cell responses to ESO in cancer patients are prevalently of TH1 type and not Treg. Their relatively low frequency and advanced differentiation stage, however, may limit their efficacy, that may be boosted by immunogenic ESO vaccines

Shockwave / foam film interaction (presenter Q. Raimbaud)

International audienc

Impact of a shock wave on a heterogeneous foam film

International audienceLiquid foams are, amongst other applications, used to mitigate shock waves. This aspect has received considerable attention at the macroscopic scale. However, the interaction between foam films and shock waves is still poorly understood and may be an important missing local information to build mitigation models. In this paper, we experimentally identify a new process leading to the foam film rupture, which dominates when the film thickness is sufficiently heterogeneous. Using a two-thickness film with a sharp and localised thickness gradient, we record the deformation of the interface between the thick and the thin parts. We observe the growth of an excess liquid area in the thin part and establish an analytical model and scaling laws which account for this phenomenon. Our results in this ideal configuration are consistent with actual rupture processes at stake in heterogeneous foam films

Impact of a shock wave on a heterogeneous foam film

Abstract </jats:p

Foam film / shock wave interaction

International audienc

CXCR3+ T Regulatory Cells Selectively Accumulate in Human Ovarian Carcinomas to Limit Type I Immunity

Abstract Antitumor type I T-cell responses involving IFN-γ production are critical to control cancer, but the efficacy of this response is limited by a variety of immunosuppressive mechanisms that promote tumoral immune escape. One critical mechanism involves the accumulation of FOXP3+ T regulatory cells (Treg), a class of suppressive T cells that prevent excessive tissue destruction caused by unchecked immune responses. Recent studies have revealed that FOXP3+ Treg include distinct subsets specifically controlling over the corresponding effector subset. In particular, CXCR3+ Treg have been described as a subset specialized in the control of type I T-cell responses in vivo. Here, we show that CXCR3+ Treg are highly enriched in human ovarian carcinomas, particularly in solid tumor masses, where they represent the majority of Treg. Tumor-associated CXCR3+. Treg coexpress T-bet but do not secrete IFN-γ ex vivo and suppress proliferation and IFN-γ secretion of T effectors. In addition, they coexpress Helios, suggesting that they originate from natural Treg. Finally, we show that the proportion of CXCR3+ Treg at tumor sites is directly correlated with that of CXCR3+ T effectors, consistent with expression of CXCR3 ligands. Together, our findings support the concept that natural CXCR3+ T-bet+ Treg selectively accumulate in ovarian tumors to control type I T-cell responses, resulting in the collateral limitation of efficient antitumor immunity. Cancer Res; 72(17); 4351–60. ©2012 AACR.</jats:p

Human memory FOXP3+ Treg secrete IL-17 <i>ex-vivo</i> and constitutively express the TH17 lineage specific transcription factor RORγt (33.14)

Abstract Recent studies have suggested a close relationship between CD4+FOXP3+ regulatory T cells (Treg) and pro-inflammatory IL-17-producing T helper cells (TH17) expressing the lineage-specific transcription factor RORγt. We report here the unexpected finding that human memory Treg secrete IL-17 ex-vivo and constitutively express RORγt. IL-17 secreting Treg share some phenotypic and functional features with conventional TH17 cells, expressing high levels of CCR4 and CCR6 and low levels of CXCR3. However, at variance with conventional TH17 cells, they express low levels of CD161 and mostly fail to co-secrete IL-22 and TNF-α ex-vivo. Ex-vivo secretion of IL-17 and constitutive expression of RORγt by human memory Treg suggest that, beside their well known suppressive functions, these cells likely play additional yet un-described pro-inflammatory functions.</jats:p

Supplementary Figure 6 from CXCR3&lt;sup&gt;+&lt;/sup&gt; T Regulatory Cells Selectively Accumulate in Human Ovarian Carcinomas to Limit Type I Immunity

&lt;p&gt;PDF file - 54K, Assessment of the expression of CCL22 in OC tumors&lt;/p&gt;</jats:p