Combined sublethal irradiation and agonist anti-CD40 enhance donor T cell accumulation and control of autochthonous murine pancreatic tumors.

Tumor-reactive T lymphocytes can promote the regression of established tumors. However, their efficacy is often limited by immunosuppressive mechanisms that block T cell accumulation or function. ACT provides the opportunity to ameliorate immune suppression prior to transfer of tumor-reactive T cells to improve the therapeutic benefit.

The TNF Receptor Superfamily in Co-stimulating and Co-inhibitory Responses.

Cytokines related to tumor necrosis factor (TNF) provide a communication network essential for coordinating multiple cell types into an effective host defense system against pathogens and malignant cells. The pathways controlled by the TNF superfamily differentiate both innate and adaptive immune cells and modulate stromal cells into microenvironments conducive to host defenses. Members of the TNF receptor superfamily activate diverse cellular functions from the production of type 1 interferons to the modulation of survival of antigen-activated T cells.

Whole-body irradiation increases the magnitude and persistence of adoptively transferred T cells associated with tumor regression in a mouse model of prostate cancer.

Adoptive immunotherapy has demonstrated efficacy in a subset of clinical and preclinical studies, but the T cells used for therapy often are rendered rapidly nonfunctional in tumor-bearing hosts. Recent evidence indicates that prostate cancer can be susceptible to immunotherapy, but most studies using autochthonous tumor models demonstrate only short-lived T-cell responses in the tolerogenic prostate microenvironment. Here, we assessed the efficacy of sublethal whole-body irradiation (WBI) to enhance the magnitude and duration of adoptively transferred CD8(+) T cells in the transgenic adenocarcinoma of the mouse prostate (TRAMP) model.

Anaplastic renal carcinoma expressing SV40 T antigen in a female TRAMP mouse.

An 8-mo-old female transgenic adenocarcinoma of the mouse prostate (C57BL/6-Tg(TRAMP)8247Ng/J) mouse presented with abdominal distention, lethargy, and serosanguineous vaginal discharge. A large primary renal tumor with metastases to lung and liver was present at necropsy. The tumor was composed of poorly differentiated and crowded epithelial cells forming ducts, acini, and cribriform patterns, with comedonecrosis and frequent bizarre mitoses.