Cd4+ T cells recovered from a mixed immune lymphocyte-tumor cell culture induce thymidine incorporation by naive rat lymphocytes in response to tumor cells

1994 ◽  
Vol 57 (2) ◽  
pp. 254-258
Author(s):  
Danièle Reisser ◽  
François Martin
Keyword(s):  
Cell Culture ◽  
T Cells ◽  
Tumor Cell ◽  
Tumor Cells ◽  
Cd4 T Cells ◽  
Thymidine Incorporation ◽  
Immune Lymphocyte ◽  
Rat Lymphocytes ◽  
Tumor Cell Culture

Dynamics of T-cell infiltration during the course of ovarian cancer: The gradual shift from a Th17 effector cell response to a predominant infiltration by regulatory T cells.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e22129-e22129
Author(s):  
Simona Partlova ◽  
Anna Fialova ◽  
Ludek Sojka ◽  
Lukas Rob ◽  
Jirina Bartunkova ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Culture ◽  
Flow Cytometry ◽  
T Cells ◽  
Regulatory T Cells ◽  
Tumor Cell ◽  
Immune Cells ◽  
Tumor Tissue ◽  
Tumor Cell Culture ◽  
Culture Supernatants

e22129 Background: Ovarian cancer is diagnosed in more than 190,000 new patients every year and is known to have the highest mortality rate among gynaecologic cancers. The type of immune cells that are present within the tumor microenvironment can play a crucial role in the survival of patients. However, little is known about the dynamics of the tumor-infiltrating immune cells during disease progression. Methods: We studied the immune cells infiltrating the tumor tissue of ovarian cancer patients at different stages of disease. We analysed the patterns of T lymphocytes in fresh tumor tissue as well as blood samples of 44 newly diagnosed ovarian cancer patients by flow cytometry. To evaluate whether regulatory T cells (Tregs) develop in situ or migrate to tumor tissue, we measured a concentration of chemokine CCL22 in tumor cell culture supernatants. We also determined the expression of CCR4 on circulating as well as tumor-infiltrating Tregs by flow cytometry. Results: The early stages of development of ovarian carcinomas were characterized by a strong Th17 immune response, whereas in stage II patients, recruitment of high numbers of Th1 cells was observed. In disseminated tumors (stage III-IV), we detected a dominant population of Helios+ activated regulatory T cells along with high numbers of macrophages and immature myeloid dendritic cells. Tumor-infiltrating Tregs had markedly lower expression of CCR4 than circulating Tregs, and the numbers of tumor-infiltrating Tregs significantly correlated with the levels of CCL22 in ovarian tumor cell culture supernatants, suggesting their recruitment via a CCR4/CCL22 interaction. CCL22 was mainly produced by tumor cells, macrophages and mDCs in the primary ovarian tumors, and its expression markedly increased in response to IFNgamma. Conclusions: Taken together, the specific recruitment of Tregs, probably triggered by inflammatory stimuli, leads to a significant immune suppression in the advanced stages of ovarian cancer.

scholarly journals Metabolic Switching of Tumor Cells under Hypoxic Conditions in a Tumor-on-a-chip Model

Micromachines ◽  
2020 ◽  
Vol 11 (4) ◽  
pp. 382 ◽  
Author(s):  
Valentina Palacio-Castañeda ◽  
Lucas Kooijman ◽  
Bastien Venzac ◽  
Wouter Verdurmen ◽  
Séverine Le Gac
Keyword(s):  
Cell Culture ◽  
Tumor Microenvironment ◽  
Tumor Cell ◽  
Tumor Cells ◽  
In Vitro Models ◽  
Cancer Therapies ◽  
Metabolic Switch ◽  
Hypoxic Conditions ◽  
Tumor Cell Culture

Hypoxia switches the metabolism of tumor cells and induces drug resistance. Currently, no therapeutic exists that effectively and specifically targets hypoxic cells in tumors. Development of such therapeutics critically depends on the availability of in vitro models that accurately recapitulate hypoxia as found in the tumor microenvironment. Here, we report on the design and validation of an easy-to-fabricate tumor-on-a-chip microfluidic platform that robustly emulates the hypoxic tumor microenvironment. The tumor-on-a-chip model consists of a central chamber for 3D tumor cell culture and two side channels for medium perfusion. The microfluidic device is fabricated from polydimethylsiloxane (PDMS), and oxygen diffusion in the device is blocked by an embedded sheet of polymethyl methacrylate (PMMA). Hypoxia was confirmed using oxygen-sensitive probes and the effect on the 3D tumor cell culture investigated by a pH-sensitive dual-labeled fluorescent dextran and a fluorescently labeled glucose analogue. In contrast to control devices without PMMA, PMMA-containing devices gave rise to decreases in oxygen and pH levels as well as an increased consumption of glucose after two days of culture, indicating a rapid metabolic switch of the tumor cells under hypoxic conditions towards increased glycolysis. This platform will open new avenues for testing anti-cancer therapies targeting hypoxic areas.

scholarly journals Single-cell evaluation reveals shifts in the tumor-immune niches that shape and maintain aggressive lesions in the breast

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Vidya C. Sinha ◽  
Amanda L. Rinkenbaugh ◽  
Mingchu Xu ◽  
Xinhui Zhou ◽  
Xiaomei Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
Mouse Model ◽  
Transition State ◽  
Tumor Cell ◽  
Single Cell ◽  
Tumor Cells ◽  
Breast Lesions ◽  
Aggressive Tumor ◽  
Insight Into

AbstractThere is an unmet clinical need for stratification of breast lesions as indolent or aggressive to tailor treatment. Here, single-cell transcriptomics and multiparametric imaging applied to a mouse model of breast cancer reveals that the aggressive tumor niche is characterized by an expanded basal-like population, specialization of tumor subpopulations, and mixed-lineage tumor cells potentially serving as a transition state between luminal and basal phenotypes. Despite vast tumor cell-intrinsic differences, aggressive and indolent tumor cells are functionally indistinguishable once isolated from their local niche, suggesting a role for non-tumor collaborators in determining aggressiveness. Aggressive lesions harbor fewer total but more suppressed-like T cells, and elevated tumor-promoting neutrophils and IL-17 signaling, disruption of which increase tumor latency and reduce the number of aggressive lesions. Our study provides insight into tumor-immune features distinguishing indolent from aggressive lesions, identifies heterogeneous populations comprising these lesions, and supports a role for IL-17 signaling in aggressive progression.

scholarly journals Cellular cytotoxicity is a form of immunogenic cell death

2020 ◽  
Vol 8 (1) ◽  
pp. e000325 ◽  
Author(s):  
Luna Minute ◽  
Alvaro Teijeira ◽  
Alfonso R Sanchez-Paulete ◽  
Maria C Ochoa ◽  
Maite Alvarez ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Death ◽  
Dendritic Cells ◽  
Tumor Cell ◽  
Tumor Cells ◽  
Cd8 T Cells ◽  
Immunogenic Cell Death ◽  
Cell Debris ◽  
Tumor Cell Death ◽  
Mhc Multimer

BackgroundThe immune response to cancer is often conceptualized with the cancer immunity cycle. An essential step in this interpretation is that antigens released by dying tumors are presented by dendritic cells to naive or memory T cells in the tumor-draining lymph nodes. Whether tumor cell death resulting from cytotoxicity, as mediated by T cells or natural killer (NK) lymphocytes, is actually immunogenic currently remains unknown.MethodsIn this study, tumor cells were killed by antigen-specific T-cell receptor (TCR) transgenic CD8 T cells or activated NK cells. Immunogenic cell death was studied analyzing the membrane exposure of calreticulin and the release of high mobility group box 1 (HMGB1) by the dying tumor cells. Furthermore, the potential immunogenicity of the tumor cell debris was evaluated in immunocompetent mice challenged with an unrelated tumor sharing only one tumor-associated antigen and by class I major histocompatibility complex (MHC)-multimer stainings. Mice deficient inBatf3,Ifnar1andSting1were used to study mechanistic requirements.ResultsWe observe in cocultures of tumor cells and effector cytotoxic cells, the presence of markers of immunogenic cell death such as calreticulin exposure and soluble HMGB1 protein. Ovalbumin (OVA)-transfected MC38 colon cancer cells, exogenously pulsed to present the gp100 epitope are killed in culture by mouse gp100-specific TCR transgenic CD8 T cells. Immunization of mice with the resulting destroyed cells induces epitope spreading as observed by detection of OVA-specific T cells by MHC multimer staining and rejection of OVA+EG7 lymphoma cells. Similar results were observed in mice immunized with cell debris generated by NK-cell mediated cytotoxicity. Mice deficient inBatf3-dependent dendritic cells (conventional dendritic cells type 1, cDC1) fail to develop an anti-OVA response when immunized with tumor cells killed by cytotoxic lymphocytes. In line with this, cultured cDC1 dendritic cells uptake and can readily cross-present antigen from cytotoxicity-killed tumor cells to cognate CD8+T lymphocytes.ConclusionThese results support that an ongoing cytotoxic antitumor immune response can lead to immunogenic tumor cell death.

scholarly journals Correlation between the mixed lymphocyte tumor cell culture reaction (MLTR) and some histological characteristics in esophageal cancer.

1980 ◽  
Vol 132 (3) ◽  
pp. 267-276
Author(s):  
YOSHIKI KURIYA ◽  
TETSURO NISHIHIRA ◽  
SHOZO MORI ◽  
TOSHIO WATANABE ◽  
TAIJI SASAKI ◽  
...  
Keyword(s):  
Cell Culture ◽  
Esophageal Cancer ◽  
Tumor Cell ◽  
Tumor Cell Culture ◽  
Histological Characteristics

scholarly journals Participation of the H-2 antigens of tumor cells in their lysis by syngeneic T cells.

1976 ◽  
Vol 143 (3) ◽  
pp. 601-614 ◽  
Author(s):  
J W Schrader ◽  
G M Edelman
Keyword(s):  
T Cells ◽  
Tumor Cell ◽  
Tumor Cells ◽  
Target Cell ◽  
Cytotoxic T Cells ◽  
Hybrid Origin ◽  
Target Cells ◽  
Cytotoxic Lymphocytes ◽  
Effector Cells

Cytotoxic T lymphocytes were generated in vitro against H-2 compatible or syngeneic tumor cells. In vitro cytotoxic activity was inhibited by specific anti-H2 sera, suggesting that H-2 antigens are involved in cell lysis. Two observations directly demonstrated the participation of the H-2 antigens on the tumor cells in their lysis by H-2-compatible T cells. First, coating of the H-2 antigens on the target tumor cell reduced the number of cells lysed on subsequent exposure to cytotoxic T cells. Second, when cytotoxic T cells were activated against an H-2 compatible tumor and assayed against an H-2-incompatible tumor, anti-H-2 serum that could bind to the target cell, but not to the cytotoxic lymphocyte, inhibited lysis. H-2 antigens were also shown to be present on the cytotoxic lymphocytes. Specific antisera reacting with these H-2 antigens, but not those of the target cell, failed to inhibit lysis when small numbers of effector cells were assayed against H-2-incompatible target cells or when effector cells of F1-hybrid origin and bearing two H-2 haplotypes were assayed against a tumor cell of one of the parental strains. These findings suggest that it is the H-2 antigens on the tumor cell and not those on the cytotoxic lymphocytes that are important in cell-mediated lysis of H-2-compatible tumor cells.

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