Permissive expansion and homing of adoptively transferred T cells in tumor-bearing hosts.

Activated T cells expressing endogenous or transduced TCRs are two cell types currently used in clinical adoptive T-cell therapy. The ability of these cells to recognize their antigen, expand and traffic to the tumor site are the initial steps necessary for successful therapy. In this study, we used in vivo bioluminescent imaging (BLI) of Renilla luciferase (RLuc) expressing T cells to evaluate the ability of adoptively transferred T cells to survive, expand and home to tumor site in vivo.

Efficacy of CAR T-cell therapy in large tumors relies upon stromal targeting by IFNγ.

Adoptive T-cell therapy using chimeric antigen receptor-modified T cells (CAR-T therapy) has shown dramatic efficacy in patients with circulating lymphoma. However, eradication of solid tumors with CAR-T therapy has not been reported yet to be efficacious. In solid tumors, stroma destruction, due to MHC-restricted cross-presentation of tumor antigens to T cells, may be essential.

Vaccine-instructed intratumoral IFN-γ enables regression of autochthonous mouse prostate cancer in allogeneic T-cell transplantation.

Vaccination can synergize with transplantation of allogeneic hematopoietic stem cells to cure hematologic malignancies, but the basis for this synergy is not understood to the degree where such approaches could be effective for treating solid tumors. We investigated this issue in a transgenic mouse model of prostate cancer treated by transplantation of a nonmyeloablative MHC-matched, single Y chromosome-encoded, or multiple minor histocompatibility antigen-mismatched hematopoietic cell preparation. Here, we report that tumor-directed vaccination after allogeneic hematopoietic stem cell transplantation and donor lymphocyte infusion is essential for acute graft versus tumor responses, tumor regression, and prolonged survival.

Fas expression by tumor stroma is required for cancer eradication.

The contribution of molecules such as perforin, IFN-γ (IFNγ), and particularly Fas ligand (FasL) by transferred CD8(+) effector T (T(E)) cells to rejection of large, established tumors is incompletely understood. Efficient attack against large tumors carrying a surrogate tumor antigen (mimicking a "passenger" mutation) by T(E) cells requires action of IFNγ on tumor stroma cells to avoid selection of antigen-loss variants. Because "cancer-driving" antigens (CDAs) are rarely counterselected, IFNγ may be expected to be dispensable in elimination of cancers by targeting a CDA.

Heme oxygenase-1 inhibits T cell-dependent skin inflammation and differentiation and function of antigen-presenting cells.

Heme oxygenase-1 (HO-1) is increased in psoriatic skin. We asked for the impact of physiological and pharmacological HO-1 induction on skin immunity and the mechanisms involved in HO-1-induced immunomodulation. We found cutaneous HO-1 expression upregulated comparable with suppressors of cytokine signalling (SOCS)1 and SOCS3 in psoriasis and atopic eczema and temporarily increased in murine ovalbumin-induced late phase reaction (LPR) and 2,4-dinitrofluorobenzene (DNFB)-induced contact hypersensitivity (CHS).