Tumor-Specific Responses in Lymph Nodes Draining Murine Sarcomas Are Concentrated in Cells Expressing P-Selectin Binding Sites

Tanigawa, Keishi; Takeshita, Nobuhiro; Craig, Ronald A.; Phillips, Katie; Knibbs, Randall N.; Chang, Alfred E.; Stoolman, Lloyd M.

doi:10.4049/jimmunol.167.6.3089

Cited by 13 publications

(6 citation statements)

References 49 publications

(44 reference statements)

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“…We have previously shown that approximately 60% of tumor-draining lymph node (TDLN) cells are CD3 + T cells. In vitro activation of TDLN cells with anti-CD3/anti-CD28 mAbs results in the generation of therapeutic effector T cells (>90% CD3 + cells) 18–21 . These effector T cells require in vivo priming with tumor, since normal lymph nodes or splenocytes from non-tumor bearing mice cannot be secondarily activated to differentiate into tumor reactive cells.…”

Section: Introductionmentioning

confidence: 99%

Adoptive Transfer of Tumor Reactive B Cells Confers Host T-Cell Immunity and Tumor Regression

Lao

Pan

et al. 2011

Clinical Cancer Research

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133

120

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Purpose We investigated the antitumor reactivity of adoptively transferred effector B cells and the mechanisms by which they may mediate tumor regression in a spontaneous metastases model. Experimental Design 4T1 breast cancer cells were inoculated into the flanks of syngeneic Balb/C mice to prime draining lymph nodes. Tumor-draining lymph nodes (TDLN) were harvested and B cells activated ex vivo with LPS and anti-CD40 mAb. These activated B cells were adoptively transferred into mice inoculated with 4T1 tumor in the mammary fat pad. The induction of host T cell immunity was evaluated. Results Activated 4T1 TDLN B cells secreted IgG in response to tumor cells which was immunologically specific. These activated B cells were capable of mediating specific lysis of tumor cells in vitro. Transfer of these activated B cells alone mediated the inhibition of spontaneous metastases to the lung. Examination of the host revealed that the transfer of these B cells resulted in the induction of tumor specific T cell immunity as measured by cytotoxicity and cytokine (IFNγ and GM-CSF) production. The combined transfer of activated T and B cells from TDLN resulted in tumor regression, which was greater than either cell population alone, with host B cells capable of producing IgG that mediated lysis of tumor in the presence of complement. Conclusions We have found that appropriately primed B cells can mediate tumor regression by itself and confers host T cell antitumor immunity. Furthermore, effector B cells can serve as a useful adjunct in adoptive T cell therapy.

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Section: Introductionmentioning

confidence: 99%

Adoptive Transfer of Tumor Reactive B Cells Confers Host T-Cell Immunity and Tumor Regression

Lao

Pan

et al. 2011

Clinical Cancer Research

Self Cite

133

120

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“…For this type of analysis, AT cells can be strongly labeled with CFSE (5 μM or greater) prior to adoptive transfer, thereby creating a neo-antigen that can be detected by anti-FITC antibodies when applied to recovered tissues (Figure 3). In this example, tumor-specific lymphocytes derived from OT-1 transgenic mice, whose T cell receptors specifically recognize an ovalbumin peptide, were activated (anti-CD3 antibody) and expanded (IL-2) ex vivo by standard protocols (Tanigawa et al, 2001). The OT-1 lymphocytes were labeled with 5 μM CFSE and injected via tail vein into mice bearing B16 melanoma tumors expressing ovalbumin (B16-OVA).…”

Section: Lymphocyte Detection During Adoptive Immunotherapy 815mentioning

confidence: 99%

Tracking the Elusive Lymphocyte: Methods of Detection during Adoptive Immunotherapy

Skitzki

Muhitch

Evans

2007

Immunological Investigations

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Adoptive immunotherapy is an attractive cancer treatment modality due to its capacity to target primary and metastatic lesions with large numbers of tumor-reactive, cytotoxic lymphocytes. The inability of fully armed lymphocytes to traffic into sites of tumor has been proposed as a causal factor for the minimal success observed clinically with this type of immunotherapy. The study of lymphocyte trafficking during adoptive immunotherapy has been limited, despite the existence of a variety of tracking methods. In murine models that simulate adoptive immunotherapy, the use of congenic mice and cell tracking dyes can be used to elucidate lymphocyte trafficking behavior. The continued development of novel technologies will further contribute to this expanding area of research.

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“…Further, CCR4 on human CD8 1 T cells can mediate migration towards melanoma cells in vitro. There are conflicting reports concerning the involvement of CXCR4 in CD8 1 T-cell infiltration of melanoma (118,119), and the roles of P-selectin and E-selectin in tumor protection (120,121).…”

Section: Expression Of Adhesion Proteins and Chemokine Receptors Aftementioning

confidence: 99%

Strategies and challenges in eliciting immunity to melanoma

Ferguson¹,

Nichols²,

Zarling³

et al. 2008

Immunological Reviews

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SummaryThe ability of CD8 T cells to recognize melanoma tumors has led to the development of immunotherapeutic approaches that use the antigens CD8 T cells recognize. However, clinical responses rates have been disappointing. Here we summarize our work to understand the mechanisms of self-tolerance that limit responses to currently utilized antigens, and our approach to identify new antigens directly tied to malignancy. We also explore several aspects of the anti-tumor immune response induced by peptide-pulsed dendritic cells. Dendritic cells differentially augment the low avidity of recall T cells specific for self-antigens, and overcome a process of aberrant CD8 T cell differentiation that occurs in tumor-draining lymph nodes. Dendritic cell migration is constrained by injection route, resulting in immune responses in localized lymphoid tissue, and differential control of tumors depending on their location in the body. We demonstrate that CD8 T cell differentiation in different lymphoid compartments alters the expression of homing receptor molecules and the presence of systemic central memory cells. Our studies highlight several issues that must be addressed to improve the efficacy of tumor immunotherapy.

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Tumor-Specific Responses in Lymph Nodes Draining Murine Sarcomas Are Concentrated in Cells Expressing P-Selectin Binding Sites

Cited by 13 publications

References 49 publications

Adoptive Transfer of Tumor Reactive B Cells Confers Host T-Cell Immunity and Tumor Regression

Adoptive Transfer of Tumor Reactive B Cells Confers Host T-Cell Immunity and Tumor Regression

Tracking the Elusive Lymphocyte: Methods of Detection during Adoptive Immunotherapy

Strategies and challenges in eliciting immunity to melanoma

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