Ineffective immune enhancement by IL-12 in tumor-bearing mice whose immune depression is mediated by suppressive granulocyte-macrophage progenitor cells

Prechel, Margaret; Lozano, Yvonne; Wright, M. A.; Ihm, Joe; Young, Matthew R.

doi:10.1016/0304-3835(95)03804-6

Cited by 5 publications

(1 citation statement)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Another significant aspect of the IL-12 antitumor effect of IL-12 in the Lewis lung cancer model is that IL-12 in conjunction with cyclophosphamide yielded a significant antitumor response over and above the primary therapy alone despite the fact this cell line is non-immunogenic. Previous reports of the effect of IL-12 on the Lewis lung cancer tumor model showed that IL-12 had no antitumor effect with this non-immunogenic tumor [ 46 ]. Thus, our results for the IL-12 pre-post treatment group in this non-immunogenic tumor, where %T/C is about 34%, suggest that the combination of chemotherapy and IL-12 altered the immunogenicity of this non-immunogenic lung cancer model.…”

Section: Resultsmentioning

confidence: 99%

Multilineage hematopoietic recovery with concomitant antitumor effects using low dose Interleukin-12 in myelosuppressed tumor-bearing mice

et al. 2008

View full text Add to dashboard Cite

Background: Interleukin-12 (IL-12) is a cytokine well known for its role in immunity. A lesser known function of IL-12 is its role in hematopoiesis. The promising data obtained in the preclinical models of antitumor immunotherapy raised hope that IL-12 could be a powerful therapeutic agent against cancer. However, excessive clinical toxicity, largely due to repeat dose regimens, and modest clinical response observed in the clinical trials have pointed to the necessity to design protocols that minimize toxicity without affecting the anti-tumor effect of IL-12. We have focused on the lesser known role of IL-12 in hematopoiesis and hypothesized that an important clinical role for IL-12 in cancer may be as an adjuvant hematological cancer therapy. In this putative clinical function, IL-12 is utilized for the prevention of cancer therapy-related cytopenias, while providing concomitant anti-tumor responses over and above responses observed with the primary therapy alone. This putative clinical function of IL-12 focuses on the dual role of IL-12 in hematopoiesis and immunity.

show abstract

Section: Resultsmentioning

confidence: 99%

Multilineage hematopoietic recovery with concomitant antitumor effects using low dose Interleukin-12 in myelosuppressed tumor-bearing mice

et al. 2008

View full text Add to dashboard Cite

show abstract

Trials and tribulations of immunotherapy as a treatment option for patients with squamous cell carcinoma of the head and neck

Young

2004

Cancer Immunology, Immunotherapy

View full text Add to dashboard Cite

Head and neck squamous cell carcinoma (HNSCC) is an aggressive epithelial malignancy that is the sixth most common neoplasm in the world. Despite numerous advances in treatments involving surgery, radiation, and chemotherapy, the 5-year survival has remained at less than 50% for the last 30 years primarily due to local recurrences [66]. Consequently, the possibility of developing immunotherapeutic approaches as a treatment for HNSCC has gained interest. The present review has 3 objectives pertaining to immunotherapeutic means to treat HNSCC patients: (1) to summarize the feasibility of such approaches, (2) to provide an overview of the obstacles to attaining protective immune reactivity, and (3) to consider how these obstacles can be overcome to stimulate immune reactivity to HNSCC. These objectives will also be considered in the context of what lessons have been learned from immunotherapeutic trials for other solid malignancies and the applicability of this information to HNSCC.

show abstract

Stimulation of immune suppressive CD34 + cells from normal bone marrow by Lewis lung carcinoma tumors

Wright

Wiers

Vellody

et al. 1998

Cancer Immunology, Immunotherapy

View full text Add to dashboard Cite

Progressive growth of metastatic Lewis lung carcinoma (LLC-LN7) tumors is associated with increased levels of bone-marrow-derived CD34+ cells having natural suppressor (NS) activity toward T cells. The present studies determined whether tumor-derived products are responsible for this induction of NS activity. Culturing normal bone marrow cells with LLC-LN7-conditioned medium (LLC-CM) or with recombinant granulocyte/macrophage-colony-stimulating factor (GM-CSF) resulted in the appearance of NS activity. The development of NS activity coincided with a prominent increase in the levels of CD34+ cells. That the CD34+ cells were responsible for the NS activity of the bone marrow cultures containing LLC-CM was shown by the loss of NS activity when CD34+ cells were depleted. The stimulation of CD34+ NS cells by LLC-CM was attributed to tumor production of GM-CSF, since neutralization of GM-CSF within the LLC-CM reduced its capacity to increase CD34+ cell levels. Studies also showed that the induction of CD34+ NS cells by LLC-CM and GM-CSF could be overcome by including in the cultures an inducer of myeloid differentiation, 1alpha,25-dihydroxyvitamin D3 [1,25(OH)2D3]. These results demonstrate that the mechanism by which the LLC-LN7 tumors stimulate increased levels of CD34+ NS cells from normal bone marrow is by their production of GM-CSF and that this can be blocked with the myeloid differentiation inducer 1,25(OH)2D3.

show abstract

Ineffective immune enhancement by IL-12 in tumor-bearing mice whose immune depression is mediated by suppressive granulocyte-macrophage progenitor cells

Cited by 5 publications

References 23 publications

Multilineage hematopoietic recovery with concomitant antitumor effects using low dose Interleukin-12 in myelosuppressed tumor-bearing mice

Multilineage hematopoietic recovery with concomitant antitumor effects using low dose Interleukin-12 in myelosuppressed tumor-bearing mice

Trials and tribulations of immunotherapy as a treatment option for patients with squamous cell carcinoma of the head and neck

Stimulation of immune suppressive CD34 + cells from normal bone marrow by Lewis lung carcinoma tumors

Contact Info

Product

Resources

About