The Experts below are selected from a list of 174597 Experts worldwide ranked by ideXlab platform

Kerstin Wennhold - One of the best experts on this subject based on the ideXlab platform.

  • CD86 Antigen presenting b cells are increased in cancer localize in tertiary lymphoid structures and induce specific t cell responses
    Cancer immunology research, 2021
    Co-Authors: Kerstin Wennhold, Axel Lechner, Martin Thelen, J Lehmann, Simon Schran, Ella Preugszat, Maria Garciamarquez, Alexander Shimabukurovornhagen, Meryem S Ercanoglu, Florian Klein
    Abstract:

    The role of B cells in antitumor immunity and their impact on emerging immunotherapies is increasingly gaining attention. B-cell effector functions include not only secretion of antibodies, but also presentation of Antigens to T cells. A physiologic B-cell subset with immunostimulatory properties was described in humans, defined by a high expression of CD86 and downregulation of CD21. We used multicolor flow cytometry and IHC to elucidate abundance and spatial distribution of these Antigen-presenting B cells (BAPC) in blood (peripheral blood mononuclear cells, PBMC) and tumor samples of 237 patients with cancer. Antigen-specific T-cell responses to cancer testis Antigens were determined using tetramer staining and sorted BAPCs in FluoroSpot assays for selected patients. We found that BAPCs were increased in the tumor microenvironment of 9 of 10 analyzed cancer types with site-specific variation. BAPCs were not increased in renal cell carcinoma, whereas we found a systemic increase with elevated fractions in tumor-infiltrating lymphocytes (TIL) and PBMCs of patients with colorectal cancer and gastroesophageal adenocarcinoma. BAPCs were localized in lymphoid follicles of tertiary lymphoid structures (TLS) and were enriched in tumors with increased numbers of TLSs. BAPCs isolated from tumor-draining lymph nodes of patients with cancer showed increased percentages of tumor Antigen-specific B cells and induced responses of autologous T cells in vitro. Our results highlight the relevance of BAPCs as professional Antigen-presenting cells in tumor immunity and provide a mechanistic rationale for the observed correlation of B-cell abundance and response to immune checkpoint inhibition.

  • tumor associated b cells and humoral immune response in head and neck squamous cell carcinoma
    OncoImmunology, 2019
    Co-Authors: Axel Lechner, Hans A Schloser, Martin Thelen, Kerstin Wennhold, Sacha I Rothschild, Ramona Gilles, A Quaas, O Siefer, Christian U Huebbers, Engin Cukuroglu
    Abstract:

    ABSTRACTB lymphocytes are important players in immune responses to cancer. However, their composition and function in head and neck squamous cell carcinoma (HNSCC) has not been well described. Here, we analyzed B cell subsets in HNSCC (n = 38), non-cancerous mucosa (n = 14) and peripheral blood from HNSCC patients (n = 38) and healthy controls (n = 20) by flow cytometry. Intratumoral B cells contained high percentages of activated (CD86+), Antigen-presenting (CD86+/CD21−) and memory B cells (IgD−/CD27+). T follicular helper cells (CD4+/CXCR5+/CD45RA−/CCR7−) as key components of tertiary lymphoid structures and plasma cells made up high percentages of the lymphocyte infiltrate. Percentages of regulatory B cell varied depending on the regulatory phenotype. Analysis of humoral immune responses against 23 tumor-associated Antigens (TAA) showed reactivity against at least one Antigen in 56% of HNSCC patients. Reactivity was less frequent in human papillomavirus associated (HPV+) patients and healthy controls c...

Florian Klein - One of the best experts on this subject based on the ideXlab platform.

  • CD86 Antigen presenting b cells are increased in cancer localize in tertiary lymphoid structures and induce specific t cell responses
    Cancer immunology research, 2021
    Co-Authors: Kerstin Wennhold, Axel Lechner, Martin Thelen, J Lehmann, Simon Schran, Ella Preugszat, Maria Garciamarquez, Alexander Shimabukurovornhagen, Meryem S Ercanoglu, Florian Klein
    Abstract:

    The role of B cells in antitumor immunity and their impact on emerging immunotherapies is increasingly gaining attention. B-cell effector functions include not only secretion of antibodies, but also presentation of Antigens to T cells. A physiologic B-cell subset with immunostimulatory properties was described in humans, defined by a high expression of CD86 and downregulation of CD21. We used multicolor flow cytometry and IHC to elucidate abundance and spatial distribution of these Antigen-presenting B cells (BAPC) in blood (peripheral blood mononuclear cells, PBMC) and tumor samples of 237 patients with cancer. Antigen-specific T-cell responses to cancer testis Antigens were determined using tetramer staining and sorted BAPCs in FluoroSpot assays for selected patients. We found that BAPCs were increased in the tumor microenvironment of 9 of 10 analyzed cancer types with site-specific variation. BAPCs were not increased in renal cell carcinoma, whereas we found a systemic increase with elevated fractions in tumor-infiltrating lymphocytes (TIL) and PBMCs of patients with colorectal cancer and gastroesophageal adenocarcinoma. BAPCs were localized in lymphoid follicles of tertiary lymphoid structures (TLS) and were enriched in tumors with increased numbers of TLSs. BAPCs isolated from tumor-draining lymph nodes of patients with cancer showed increased percentages of tumor Antigen-specific B cells and induced responses of autologous T cells in vitro. Our results highlight the relevance of BAPCs as professional Antigen-presenting cells in tumor immunity and provide a mechanistic rationale for the observed correlation of B-cell abundance and response to immune checkpoint inhibition.

Swarnima Singh - One of the best experts on this subject based on the ideXlab platform.

  • chemotherapy coupled to macrophage inhibition leads to b cell mediated t cell memory activation and durable triple negative breast cancer regression
    bioRxiv, 2021
    Co-Authors: Swarnima Singh, Nigel Lee, Igor Bado, Clark Hamor, Sergio Aguirre, D Pedroza, Licheng Zhang, Yichao Shen, Yang Gao, Na Zhao
    Abstract:

    Immunosuppressive elements within the tumor microenvironment such as Tumor Associated Macrophages (TAMs) can present a barrier to successful anti-tumor responses by cytolytic T cells. We employed preclinical syngeneic p53 null mouse models of TNBC to develop a treatment regimen that harnessed the immunostimulatory effects of low-dose chemotherapy coupled with the pharmacologic inhibition of TAMs. Combination therapy was used to successfully treat several highly aggressive, claudin-low murine mammary tumors and lung metastasis. Long-term responders developed tertiary lymphoid structures co-infiltrated by T and B cells at the treatment site. Mechanistically, CD86+ Antigen-experienced T cells exhibited polyclonal expansion and resulted in exceptional responses upon tumor rechallenge. Combination treatment also eliminated lung metastases. High dimensional transcriptomic data for CD45+ immune cells lead to the identification of an aberrant developmental trajectory for TAMs that were resistant to treatment. Signatures derived from these TAM populations were predictive of patient response to our therapy. This study illustrates the complexity of tumor infiltrating myeloid cells and highlights the importance of personalized immuno-genomics to inform therapeutic regimens.

  • synergy of chemotherapy and macrophage depletion leads to t cell memory activation and durable triple negative breast cancer regression
    bioRxiv, 2021
    Co-Authors: Swarnima Singh, Nigel Lee, Igor Bado, Clark Hamor, Lili Zhang, Sergio Aguirre, Yufeng Shen, Yipeng Gao, D Pedroza, N Zhan
    Abstract:

    Abstract Immunosuppressive elements within the tumor microenvironment such as Tumor Associated Macrophages (TAMs) can present a barrier to successful anti-tumor responses by cytolytic T cells. We employed preclinical syngeneic p53 null mouse models of TNBC to develop a treatment regimen that harnessed the immunostimulatory effects of low-dose chemotherapy coupled with the pharmacologic inhibition of TAMs. Combination therapy was used to successfully treat several highly aggressive, claudin-low murine mammary tumors and lung metastasis. Long-term responders developed tertiary lymphoid structures co-infiltrated by T and B cells at the treatment site. Mechanistically, CD86+ Antigen-experienced T cells exhibited polyclonal expansion and resulted in exceptional responses upon tumor rechallenge. Combination treatment also eliminated lung metastases. High dimensional transcriptomic data for CD45+ immune cells lead to the identification of an aberrant developmental trajectory for TAMs that were resistant to treatment. Signatures derived from these TAM populations were predictive of patient response to our therapy. This study illustrates the complexity of tumor infiltrating myeloid cells and highlights the importance of personalized immuno-genomics to inform therapeutic regimens. Statement of significance Triple negative breast cancer is aggressive and hard to treat as it has no targeted therapies. Targeting immunosuppressive macrophages in murine models of TNBC alongside an immunostimulatory chemotherapy achieved long-term primary tumor regression in multiple murine mouse models. The transcriptomic heterogeneity between TAMs in phenotypically similar models can be used to uncover future therapeutic targets. Additionally, signatures derived from these murine models can be applied to TNBC patient data sets to predict cohorts of patients that will respond to the treatment strategy.

Axel Lechner - One of the best experts on this subject based on the ideXlab platform.

  • CD86 Antigen presenting b cells are increased in cancer localize in tertiary lymphoid structures and induce specific t cell responses
    Cancer immunology research, 2021
    Co-Authors: Kerstin Wennhold, Axel Lechner, Martin Thelen, J Lehmann, Simon Schran, Ella Preugszat, Maria Garciamarquez, Alexander Shimabukurovornhagen, Meryem S Ercanoglu, Florian Klein
    Abstract:

    The role of B cells in antitumor immunity and their impact on emerging immunotherapies is increasingly gaining attention. B-cell effector functions include not only secretion of antibodies, but also presentation of Antigens to T cells. A physiologic B-cell subset with immunostimulatory properties was described in humans, defined by a high expression of CD86 and downregulation of CD21. We used multicolor flow cytometry and IHC to elucidate abundance and spatial distribution of these Antigen-presenting B cells (BAPC) in blood (peripheral blood mononuclear cells, PBMC) and tumor samples of 237 patients with cancer. Antigen-specific T-cell responses to cancer testis Antigens were determined using tetramer staining and sorted BAPCs in FluoroSpot assays for selected patients. We found that BAPCs were increased in the tumor microenvironment of 9 of 10 analyzed cancer types with site-specific variation. BAPCs were not increased in renal cell carcinoma, whereas we found a systemic increase with elevated fractions in tumor-infiltrating lymphocytes (TIL) and PBMCs of patients with colorectal cancer and gastroesophageal adenocarcinoma. BAPCs were localized in lymphoid follicles of tertiary lymphoid structures (TLS) and were enriched in tumors with increased numbers of TLSs. BAPCs isolated from tumor-draining lymph nodes of patients with cancer showed increased percentages of tumor Antigen-specific B cells and induced responses of autologous T cells in vitro. Our results highlight the relevance of BAPCs as professional Antigen-presenting cells in tumor immunity and provide a mechanistic rationale for the observed correlation of B-cell abundance and response to immune checkpoint inhibition.

  • tumor associated b cells and humoral immune response in head and neck squamous cell carcinoma
    OncoImmunology, 2019
    Co-Authors: Axel Lechner, Hans A Schloser, Martin Thelen, Kerstin Wennhold, Sacha I Rothschild, Ramona Gilles, A Quaas, O Siefer, Christian U Huebbers, Engin Cukuroglu
    Abstract:

    ABSTRACTB lymphocytes are important players in immune responses to cancer. However, their composition and function in head and neck squamous cell carcinoma (HNSCC) has not been well described. Here, we analyzed B cell subsets in HNSCC (n = 38), non-cancerous mucosa (n = 14) and peripheral blood from HNSCC patients (n = 38) and healthy controls (n = 20) by flow cytometry. Intratumoral B cells contained high percentages of activated (CD86+), Antigen-presenting (CD86+/CD21−) and memory B cells (IgD−/CD27+). T follicular helper cells (CD4+/CXCR5+/CD45RA−/CCR7−) as key components of tertiary lymphoid structures and plasma cells made up high percentages of the lymphocyte infiltrate. Percentages of regulatory B cell varied depending on the regulatory phenotype. Analysis of humoral immune responses against 23 tumor-associated Antigens (TAA) showed reactivity against at least one Antigen in 56% of HNSCC patients. Reactivity was less frequent in human papillomavirus associated (HPV+) patients and healthy controls c...

Martin Thelen - One of the best experts on this subject based on the ideXlab platform.

  • CD86 Antigen presenting b cells are increased in cancer localize in tertiary lymphoid structures and induce specific t cell responses
    Cancer immunology research, 2021
    Co-Authors: Kerstin Wennhold, Axel Lechner, Martin Thelen, J Lehmann, Simon Schran, Ella Preugszat, Maria Garciamarquez, Alexander Shimabukurovornhagen, Meryem S Ercanoglu, Florian Klein
    Abstract:

    The role of B cells in antitumor immunity and their impact on emerging immunotherapies is increasingly gaining attention. B-cell effector functions include not only secretion of antibodies, but also presentation of Antigens to T cells. A physiologic B-cell subset with immunostimulatory properties was described in humans, defined by a high expression of CD86 and downregulation of CD21. We used multicolor flow cytometry and IHC to elucidate abundance and spatial distribution of these Antigen-presenting B cells (BAPC) in blood (peripheral blood mononuclear cells, PBMC) and tumor samples of 237 patients with cancer. Antigen-specific T-cell responses to cancer testis Antigens were determined using tetramer staining and sorted BAPCs in FluoroSpot assays for selected patients. We found that BAPCs were increased in the tumor microenvironment of 9 of 10 analyzed cancer types with site-specific variation. BAPCs were not increased in renal cell carcinoma, whereas we found a systemic increase with elevated fractions in tumor-infiltrating lymphocytes (TIL) and PBMCs of patients with colorectal cancer and gastroesophageal adenocarcinoma. BAPCs were localized in lymphoid follicles of tertiary lymphoid structures (TLS) and were enriched in tumors with increased numbers of TLSs. BAPCs isolated from tumor-draining lymph nodes of patients with cancer showed increased percentages of tumor Antigen-specific B cells and induced responses of autologous T cells in vitro. Our results highlight the relevance of BAPCs as professional Antigen-presenting cells in tumor immunity and provide a mechanistic rationale for the observed correlation of B-cell abundance and response to immune checkpoint inhibition.

  • tumor associated b cells and humoral immune response in head and neck squamous cell carcinoma
    OncoImmunology, 2019
    Co-Authors: Axel Lechner, Hans A Schloser, Martin Thelen, Kerstin Wennhold, Sacha I Rothschild, Ramona Gilles, A Quaas, O Siefer, Christian U Huebbers, Engin Cukuroglu
    Abstract:

    ABSTRACTB lymphocytes are important players in immune responses to cancer. However, their composition and function in head and neck squamous cell carcinoma (HNSCC) has not been well described. Here, we analyzed B cell subsets in HNSCC (n = 38), non-cancerous mucosa (n = 14) and peripheral blood from HNSCC patients (n = 38) and healthy controls (n = 20) by flow cytometry. Intratumoral B cells contained high percentages of activated (CD86+), Antigen-presenting (CD86+/CD21−) and memory B cells (IgD−/CD27+). T follicular helper cells (CD4+/CXCR5+/CD45RA−/CCR7−) as key components of tertiary lymphoid structures and plasma cells made up high percentages of the lymphocyte infiltrate. Percentages of regulatory B cell varied depending on the regulatory phenotype. Analysis of humoral immune responses against 23 tumor-associated Antigens (TAA) showed reactivity against at least one Antigen in 56% of HNSCC patients. Reactivity was less frequent in human papillomavirus associated (HPV+) patients and healthy controls c...