Small numbers of residual tumor cells at the site of primary inoculation are critical for anti-tumor immunity following challenge at a secondary location

Abstract

Luciferase-transduced B16 murine melanoma cells (luc-B16) inoculated in ear skin do not form tumors but prevent tumor formation by luc-B16 cells injected into the footpad. To determine the requirements for such immunity, we followed the fate of luc-B16 cells following ear injection. Surprisingly, small numbers of viable luc-B16 cells were detected in tumor-free mouse skin for up to 60 days post-inoculation. After 1 week, the number of Foxp3(+)CD4(+)CD25(+) T cells (along with foxp3 mRNA expression) increased rapidly in the injected ear skin. Residual tumor cells in ears were reduced in mice treated with anti-CD25 mAb and in CD4-deficient mice, but increased in CD8-deficient mice. Strikingly, the loss of luc-B16 cells in the ear skin, either spontaneously or following amputation of the injected ear, resulted in significantly enhanced tumor formation by parental and luciferase-expressing B16 cells after footpad injection. These studies suggest that small numbers of tumor cells (possibly regulated by CD4(+)CD25(+) regulatory T cells expressing Foxp3) are required for effective host anti-tumor responses at alternate inoculation sites.

Multicolor Imaging of Lymphatic Function with Two Nanomaterials: Quantum Dot-Labeled Cancer Cells and Dendrimer-Based Optical Agents

“…For cell tracking we employed a melanoma cell line, B16CXCR4, that has been stably transfected with the chemokine receptor CXCR4 gene to a parental B16 melanoma cell line [16]. The presence of CXCR4 enhances in vivo cell migration leading to early metastases [17].…”

“…The B16 cell line was stably transfected with CXCR4 as previously reported [16], selected by neomycin and cloned to create the B16CXCR4 cell line, which highly expresses the CXCR4 gene and shows enhanced cell migration.…”

Correlation between FOXP3 expression and gastric cancer

“…It has been previously demonstrated that the level and function of regulatory T cells in the majority of gastric cancer patients may be useful to predict patient survival and prognosis (25). FOXP3 is an important protein marker of regulatory T cells, which exhibits important functions in development and maturation of regulatory T cells (3).…”

Clinical opportunities in combining immunotherapy with radiation therapy

“…However, this basic view is still not a complete picture of microenvironmental changes within tumor-associated endothelial cells, inflammatory infiltrates, or of systemic responses to the tumor. Areas of higher dose exposure, for example adjacent to brachytherapy seeds, or at hot-spots inside the bulk of the tumor may have markedly different pathways to cell death, emphasizing necrotic mechanisms not apoptotic ones (Nagorsen et al, 2003; Overwijk et al, 2003; Finkelstein et al, 2004; Klebanoff et al, 2004; Kakinuma et al, 2007). Additionally, the time course of changes of antigen expression by the irradiated cells may be relevant, with different patterns that are dependent on radiotherapy techniques’ dose-rate and energy level (Finkelstein et al, 2011).…”