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| 2. |
- Carlson, Lena-Maria, et al.
(författare)
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The microenvironment of human neuroblastoma supports the activation of tumor-associated T lymphocytes.
- 2013
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Ingår i: Oncoimmunology. - : Informa UK Limited. - 2162-4011 .- 2162-402X. ; 2:3
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Tidskriftsartikel (refereegranskat)abstract
- Tumor infiltration by lymphocytes has been linked to improved clinical outcome in children with neuroblastoma (NB) but T-cell activation has never been demonstrated to occur within the NB microenvironment. Here we show that tumor-associated lymphocytes (TALs) obtained from lesions representing all genetic subsets of NB and autologous peripheral blood lymphocytes (PBLs) analyzed on the day of tumor excision differed in composition, phenotype and functional characteristics. The NB microenvironment appeared to promote the accumulation of CD3(+)CD8(+) T cells and contained a larger proportion of T cells expressing the interleukin-2 receptor α chain (CD25) and manifesting an effector memory (CCR7(-)CD45RA(-)) phenotype. Accordingly, the stimulation of PBLs with autologous tumor cells in short-term cultures increased the proportion of effector memory T cells, upregulated CD25, stimulated the expression of the TH1 cytokines interferon γ and tumor necrosis factor α, and reduced the expression of transforming growth factor β. In situ proliferation as well as a characteristic pattern of T-cell receptor aggregation at the contact sites with malignant cells was revealed by the immunohistochemical staining of TALs in primary tumors, indicating that the NB milieu is compatible with the activation of the immune system. Our results are compatible with the hypothesis that CD8(+) T cells are specifically activated within the NB microenvironment, which appears to be permissive for effector memory responses.
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| 3. |
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| 4. |
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| 5. |
- Edin, Sofia, et al.
(författare)
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Macrophages : Good guys in colorectal cancer
- 2013
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Ingår i: Oncoimmunology. - : Informa UK Limited. - 2162-4011 .- 2162-402X. ; 2:2, s. e23038-
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Tidskriftsartikel (refereegranskat)abstract
- Macrophages play a complex role in tumor progression since they can exert both tumor-preventing (M1 macrophages) and tumor-promoting (M2 macrophages) activities. In colorectal carcinoma (CRC), at odds to many other cancers, macrophage infiltration has been correlated with an improved patient survival. In a recent study, we have evaluated the distribution of M1 and M2 macrophage subtypes in CRC and their impact on patient prognosis.
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| 11. |
- Klein, G
(författare)
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Tumor resistance
- 2012
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Ingår i: Oncoimmunology. - : Informa UK Limited. - 2162-4011 .- 2162-402X. ; 1:8, s. 1355-1359
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Tidskriftsartikel (refereegranskat)
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| 12. |
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| 13. |
- Leanderson, Tomas, et al.
(författare)
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S100A9 and tumor growth.
- 2012
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Ingår i: OncoImmunology. - : Informa UK Limited. - 2162-4011 .- 2162-402X. ; 1:8, s. 1404-1405
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Tidskriftsartikel (refereegranskat)abstract
- We have investigated the role of the Ca(2+)-binding protein S100A9 on tumor growth in prostate cancer and T-cell lymphoma models. We found that the expression of, S100A9 and its interaction with Toll-like receptor 4 (TLR4) is critical for tumor growth in these settings.
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| 14. |
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| 15. |
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| 16. |
- Marits, Per, et al.
(författare)
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The many flavors of tumor-associated B cells
- 2013
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Ingår i: Oncoimmunology. - : Landes Bioscience. - 2162-4011 .- 2162-402X. ; 2:8, s. e25237-
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Tidskriftsartikel (refereegranskat)abstract
- Little is known on the role of distinct B-cell subtypes in human malignancies. We have recently performed a multiplex characterization of B cells in patient-derived tumor-associated tissues, documenting the activation and antigen-driven differentiation of B cells in metastatic lymph nodes and neoplastic lesions. Here we discuss the role of B lymphocytes as antigen-presenting cells and catalysts of T cell-based immunotherapies in view of these findings.
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| 17. |
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| 18. |
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| 19. |
- Rosén, Anders, et al.
(författare)
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Lymphoblastoid cell line with B1 cell characteristics established from a chronic lymphocytic leukemia clone by in vitro EBV infection
- 2012
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Ingår i: Oncoimmunology. - : Informa UK Limited. - 2162-4011 .- 2162-402X. ; 1:1, s. 18-27
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Tidskriftsartikel (refereegranskat)abstract
- Chronic lymphocytic leukemia (CLL) cells express the receptor for Epstein-Barr virus (EBV) and can be infected in vitro. Infected cells do not express the growth-promoting set of EBV-encoded genes and therefore they do not yield LCLs, in most experiments. With exceptional clones, lines were obtained however. We describe a new line, HG3, established by in vitro EBV-infection from an IGHV1-2 unmutated CLL patient clone. All cells expressed EBNA-2 and LMP-1, the EBV-encoded genes pivotal for transformation. The karyotype, FISH cytogenetics and SNP-array profile of the line and the patient's ex vivo clone showed biallelic 13q14 deletions with genomic loss of DLEU7, miR15a/miR16-1, the two micro-RNAs that are deleted in 50% of CLL cases. Further features of CLL cells were: expression of CD5/CD20/CD27/CD43 and release of IgM natural antibodies reacting with oxLDL-like epitopes on apoptotic cells (cf. stereotyped subset-1). Comparison with two LCLs established from normal B cells showed 32 genes expressed at higher levels (> 2-fold). Among these were LHX2 and LILRA. These genes may play a role in the development of the disease. LHX2 expression was shown in self-renewing multipotent hematopoietic stem cells, and LILRA4 codes for a receptor for bone marrow stromal cell antigen-2 that contributes to B cell development. Twenty-four genes were expressed at lower levels, among these PARD3 that is essential for asymmetric cell division. These genes may contribute to establish precursors of CLL clones by regulation of cellular phenotype in the hematopoietic compartment. Expression of CD5/CD20/CD27/CD43 and spontaneous production of natural antibodies may identify the CLL cell as a self-renewing B1 lymphocyte.
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| 20. |
- Sandin, Linda C., et al.
(författare)
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Local CTLA4 blockade effectively restrains experimental pancreatic adenocarcinoma growth in vivo
- 2014
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Ingår i: Oncoimmunology. - : Informa UK Limited. - 2162-4011 .- 2162-402X. ; 3:1, s. e2761-
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Tidskriftsartikel (refereegranskat)abstract
- Antibody-mediated blockade of CTLA4 has been shown to be effective in treating a select group of patients with late-stage melanoma. The precise mechanism underlying the clinical activity of CTLA4 immunotherapy is poorly understood, although recent experimental findings indicate that antibody-mediated depletion of regulatory T cells (Tregs) in the tumor microenvironment plays a key role in efficacious antitumor responses. In the current study, we used an experimental model of pancreatic adenocarcinoma to compare the antitumor efficacy of peritumoral low-dose anti-CTLA4 monoclonal antibody (mAb) administration to that of a commonly utilized systemic high-dose anti-CTLA4 regimen. We selected pancreatic adenocarcinoma as it presents a particular challenge to clinicians due to its aggressive behavior, metastatic spread and limited treatment options. Furthermore, Fc gamma receptor (Fc gamma R)-dense myeloid cells commonly infiltrate pancreatic tumors, such that these tumor types exhibit increased susceptibility to CTLA4 antibody-targeted Treg depletion via antibody-dependent cell-mediated cytotoxicity (ADCC). Locally administered anti-CTLA4 mAb effectively reduced tumor growth at a low dose and no additional anti-tumor effects were apparent when increasing the dose or number of injections. No significant difference in overall survival was seen when comparing locally administered low-dose with standard systemic high-dose CTLA4 blockade therapy, and both delivery routes led to increased tumor-infiltrating effector T cells and reduced Treg cells. As opposed to low-dose peritumoral treatment, high-dose systemic therapy stimulated the accumulation of Tregs in secondary lymphoid organs, an effect that could potentially counteract the antitumor immunotherapeutic benefit of CTLA4 blockade. Our study confirms previous findings that local administration of low-dose anti-CTLA4 antibody generates sustained antitumor effects and provides rationale to devise ultrasound-guided intratumoral anti-CTLA4 antibody injection regimens to treat patients with pancreatic adenocarcinoma and other types of solid tumors. In support, clinical relevancy could include reduced immune-related adverse events by limiting systemic antibody spread to immune cell-dense organs.
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| 21. |
- Sandin, Linda C., et al.
(författare)
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Local immunotherapy based on agonistic CD40 antibodies effectively inhibits experimental bladder cancer
- 2014
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Ingår i: Oncoimmunology. - : Informa UK Limited. - 2162-4011 .- 2162-402X. ; 3:2
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Local immunotherapy resurfaces in the field of cancer as a potential way to cure localized and metastatic disease with limited toxic effects. We have recently demonstrated that local administration of agonistic CD40 antibodies can cure localized as well as disseminated bladder neoplasms. This approach reduces the circulating concentrations of antibodies that would result from systemic delivery, hence resulting in limited toxicity.
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| 22. |
- Schmidt, Marcus, et al.
(författare)
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Immunoglobulin kappa chain as an immunologic biomarker of prognosis and chemotherapy response in solid tumors
- 2012
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Ingår i: Oncoimmunology. - : Informa UK Limited. - 2162-4011 .- 2162-402X. ; 1:7, s. 1156-1158
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Tidskriftsartikel (refereegranskat)abstract
- Infiltration of plasma cells is associated with better prognosis in breast, lung and colon cancer. Immunoglobulin κ chain (IGKC) is now available as a single, robust immune marker predicting metastasis-free survival and response to chemotherapy. This will facilitate a deeper understanding of the role of the humoral immune system in cancer development.
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| 23. |
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| 24. |
- Weber, Alexander Nr, et al.
(författare)
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Toll-like receptor genetic variants and colorectal cancer.
- 2014
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Ingår i: OncoImmunology. - : Informa UK Limited. - 2162-4011 .- 2162-402X. ; 3:1, s. 27763-27763
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Tidskriftsartikel (refereegranskat)abstract
- Single-nucleotide polymorphisms in Toll-like receptor 5 (TLR5), encoding a sensor for flagellin, have been shown to influence cytokine responses to intestinal bacteria and to be associated with significant alterations in the survival of colorectal carcinoma (CRC) patients. These findings point to a link between TLRs and CRC that may have both therapeutic and prognostic/predictive implications.
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| 25. |
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