Masters of Immunology
Thomas Marichal, Mindy Tsai and Stephen J. Galli
Cancer Immunol Res November 1 2013 1 (5) 269-279; DOI:10.1158/2326-6066.CIR-13-0119
Analyzing samples from patients with primary clear cell renal cell carcinoma (ccRCC), Dannenmann and colleagues identified naturally occurring, polyfunctional Cyclin D1-specific CD8+ T cells from patients with Cyclin-D1+ tumors, and they propose to develop Cyclin D1 as a target for immunotherapy in patients with ccRCC.
Baia, Caballero, and colleagues found that NY-ESO-1 is the most frequently expressed cancer/testis antigen in meningioma tumors, and its expression positively correlates with higher-grade disease and worst prognosis. NY-ESO-1 proteins elicit spontaneous humoral immune responses; the authors propose that NY-ESO-1–based immunotherapy should be explored as a complement to standard therapy for patients with meningioma.
CD4+ T effector cells specific for the tumor antigen NY-ESO-1 were found to accumulate at ovarian cancer tumor sites; they maintain an effector phenotype/function and remain distinct from Treg, even when Treg are present at high proportions. These findings encourage the use of combination therapies aiming at enhancing tumor antigen-specific immune responses and eliminating or inactivating Treg.
Workenhe and colleagues show that the combination regimen of oncolytic virus with mitoxantrone significantly increases the efficacy of either treatment alone by enhancing the immunogenicity of and breaking immune tolerance against tumor-associated antigens, an Achilles' heel of current cancer therapy.
Schaer and colleagues show that GITR ligation by agonist antibody DTA-1 inhibits intratumor immune suppression by inducing tumor-dependent loss of Foxp3 and altered expression of transcription factors and cytokines important for Treg function, resulting in impaired Treg lineage stability and enhanced killing of tumor cells by T effectors. These results will inform the effective use of GITR therapy in humans.
A melanoma-specific peptide vaccine in Montanide ISA-51 induces tumor-infiltrating CD8+ T cells expressing CXCR3, with a subpopulation coexpressing CLA, both of which are associated with skin homing and are increased by GM-CSF. The authors hypothesize that specific modifications of the metastatic tumor microenvironment to elicit chemoattraction of vaccine-induced T cells would enhance vaccine efficacy for disseminated metastases.
In a comprehensive analysis of what contributes to the integrated immune responses elicited by the vaccination of ovarian cancer patients with OLP from tumor antigen NY-ESO-1, Tsuji and colleagues show that Montanide ISA-51 is critical for the expansion of high-avidity antigeninduced CD4+ T cells, and a TLR ligand poly-ICLC accelerates the induction and differentiation of vaccine-induced antigen-specific Th1 cells.