Search results for "Tumor-Infiltrating"
showing 10 items of 78 documents
Editorial: Understanding Gamma Delta T Cell Multifunctionality - Towards Immunotherapeutic Applications.
2020
Introduction: gd T cells have been characterized by the expression of a gd T cell receptor (TCR).When the gd TCR and the corresponding ab TCR were first discovered it was assumed that the corresponding cell types were likely to be functionally very similar. However, some 30 years later, we have realized that they are not. Unlike ab T cells, gd T cells (i) sense target antigens independent of MHC molecules; (ii) display NK-cell like innate reactivities, including killing of infected cells as well as microbes; (iii) are able to take up large particulates, including bacteria, and (iv) can act as professional antigen presenting cells. The “stress sensing” abilities of gd T cells have led to a g…
γδ cells and tumor microenvironment: A helpful or a dangerous liason?
2017
Abstract γδ T cells are a subset of T lymphocytes that have been implicated in immunosurveillance against infections and tumors. γδ T cells are endowed with antitumor activities, and hence several γδ T cell-based small-scale clinical trials have been conducted either by in vivo activation by intravenous administration of aminobiphosphonates or by adoptive transfer of in vitro expanded γδ T cells. Although both these strategies have yielded promising results, there are a number of limitations associated with each of them which, if overcome may help to further improve efficacy. One of the most important limits is the possible polarization of tumor-infiltrating γδ T cells toward different γδ T…
mTOR Inhibition Improves Antitumor Effects of Vaccination with Antigen-Encoding RNA
2013
Abstract Vaccination with in vitro transcribed RNA encoding tumor antigens is an emerging approach in cancer immunotherapy. Attempting to further improve RNA vaccine efficacy, we have explored combining RNA with immunomodulators such as rapamycin. Rapamycin, the inhibitor of mTOR, was used originally for immunosuppression. Recent reports in mouse systems, however, suggest that mTOR inhibition may enhance the formation and differentiation of the memory CD8+ T-cell pool. Because memory T-cell formation is critical to the outcome of vaccination aproaches, we studied the impact of rapamycin on the in vivo primed RNA vaccine-induced immune response using the chicken ovalbumin-expressing B16 mela…
Red wine extract disrupts Th17 lymphocyte differentiation in a colorectal cancer context
2020
International audience; Scope: Scope: It is well established that immune response and inflammation promote tumoral progression. Immune cells communicate through direct contact or through cytokine secretion, and it is the pro-inflammatory status that will tip the balance toward tumor progression or anti-tumor immunity. It is demonstrated here that a red wine extract (RWE) can decrease inflammation through its action on the inflammasome complex. This study determines whether an RWE could impact other key actors of inflammation, including T helper 17 (Th17) immune cells in particular. Methods and results: Methods and results: Using an RWE containing 4.16 g of polyphenols/liter of wine, it is s…
Gemcitabine, oxaliplatin, levofolinate, 5-fluorouracil, granulocyte-macrophage colony-stimulating factor, and interleukin-2 (GOLFIG) versus FOLFOX ch…
2013
The GOLFIG-2 phase III trial was designed to compare the immunobiological activity and antitumor efficacy of GOLFIG chemoimmunotherapy regimen with standard FOLFOX-4 chemotherapy in frontline treatment of metastatic colorectal cancer (mCRC) patients. This trial was conceived on the basis of previous evidence of antitumor and immunomodulating activity of the GOLFIG regimen in mCRC. GOLFIG-2 is a multicentric open/ label phase III trial (EUDRACT: 2005-003458-81). Chemo-naive mCRC patients were randomized in a 1:1 ratio to receive biweekly standard FOLFOX-4 or GOLFIG [gemcitabine (1000 mg/m 2, day 1); oxaliplatin (85 mg/m2, day 2); levofolinate (100 mg/m2, days 1-2), 5-fluorouracil (5-FU) (400…
Exome Sequencing to Predict Neoantigens in Melanoma
2015
Abstract The ability to use circulating peripheral blood cells and matched tumor sequencing data as a basis for neoantigen prediction has exciting possibilities for application in the personalized treatment of cancer patients. We have used a high-throughput screening approach, combining whole-exome sequence data, mRNA microarrays, and publicly available epitope prediction algorithm output to identify mutated proteins processed and displayed by patient tumors and recognized by circulating immune cells. Matched autologous melanoma cell lines and peripheral blood mononuclear cells were used to create mixed lymphocyte tumor cell cultures, resulting in an expansion of tumor-reactive T cells to u…
Surface phenotype and functions of tumor-infiltrating dendritic cells: CD8 expression by a cell subpopulation.
1993
Although the function and significance of tumor-infiltrating dendritic cells (TIDC) in the immune response to tumor have never been clearly demonstrated, their location suggests that they play a critical role in the presentation of tumor antigen to specific T cells. We studied the morphological and functional characteristics of interstitial dendritic cells (DC) located inside tumors obtained by injection of cancer cells into syngeneic rats. Single and double immunostaining of tumor sections revealed a dense network of cells which expressed class II major histocompatibility complex (MHC II) molecules. Cell morphology and surface markers were characteristic of DC populations in other tissues.…
Stat3 and Gfi-1 Transcription Factors Control Th17 Cell Immunosuppressive Activity via the Regulation of Ectonucleotidase Expression
2012
International audience; Although Th17 cells are known to promote tissue inflammation and autoimmunity, their role during cancer progression remains elusive. Here, we showed that in vitro Th17 cells generated with the cytokines IL-6 and TGF-β expressed CD39 and CD73 ectonucleotidases, leading to adenosine release and the subsequent suppression of CD4(+) and CD8(+) T cell effector functions. The IL-6-mediated activation of the transcription factor Stat3 and the TGF-β-driven downregulation of Gfi-1 transcription factor were both essential for the expression of ectonucleotidases during Th17 cell differentiation. Stat3 supported whereas Gfi-1 repressed CD39 and CD73 expression by binding to thei…
Tumor Lipids of Pediatric Papillary Renal Cell Carcinoma Stimulate Unconventional T Cells
2020
Papillary renal cell carcinoma (PRCC) is a rare entity in children with no established therapy protocols for advanced diseases. Immunotherapy is emerging as an important therapeutic tool for childhood cancer. Tumor cells can be recognized and killed by conventional and unconventional T cells. Unconventional T cells are able to recognize lipid antigens presented via CD1 molecules independently from major histocompatibility complex, which offers new alternatives for cancer immunotherapies. The nature of those lipids is largely unknown and α-galactosylceramide is currently used as a synthetic model antigen. In this work, we analyzed infiltrating lymphocytes of two pediatric PRCCs using flow cy…
Combined prognostic value of CD274 (PD-L1)/PDCDI (PD-1) expression and immune cell infiltration in colorectal cancer as per mismatch repair status
2019
The CD274 (programmed cell death ligand-1, PD-L1)/PDCD1 (programmed cell death-1, PD-1) pathway is crucial suppressor of the cytotoxic immune response. Antibodies targeting CD274 or PDCD1 have been revealed to be effective in several malignancies. In colorectal cancer, the response to CD274/PDCD1 blockage is associated with microsatellite instability. However, the value of CD274/PDCD1 for predicting response to treatment or survival benefit is still unclear. The aims of the study were (1) to clarify differences in immune microenvironment and expression of checkpoint proteins (CD274/PDCD1) in DNA mismatch repair-proficient, mismatch repair-deficient, and hereditary Lynch syndrome-associated …