CD4+ T Cell-Mediated Antigen-Specific Immunotherapy in a Mouse Model of Cervical Cancer

Abstract

A major agenda for tumor immunology is the generation of specific immune responses leading to the destruction of incipient and frank neoplasia. In this report, we show that a novel HPV16 E7 fusion protein can produce objective therapeutic responses against incipient cervical cancer in genetically engineered mice that express in the cervix the HPV16 early region genes implicated as causative agents in human cervical cancer. Although nonresponsive toward the HPV16 E7 oncoprotein in the CD8 + + + T-cell compartment by virtue of MHC haplotype, the mice were capable of mounting an induced CD4 + + + T-cell response against E7, and in addition developed spontaneous anti-E7 antibodies. HPV16/CD4

Clinical Relevance of Matrix Metalloproteases and their Inhibitors in Breast Cancer

“…Historically, tumorinfiltrating leukocytes have been considered to be manifestations of an intrinsic defense mechanism against developing tumors [128,129]. However, our data are in accordance with the increasing evidences indicating that leukocyte infiltration can promote tumor phenotypes, such as angiogenesis, growth and invasion [127,130]. This may be due to inflammatory cells, which secrete cytokines, growth factors, chemokines and proteases, stimulating cancer cell proliferation and invasiveness [131].…”

The biology of personalized cancer medicine: Facing individual complexities underlying hallmark capabilities

“…While less advanced in regard to appreciating individual variability, one can envision that the abundance and characteristics of these and other types of inflammatory cells will indeed prove to be deterministic and hence important parameters for personalized diagnosis. Moreover, there is increasing evidence that the bioeffector functions and hence pro‐ versus antitumor activities of both lymphoid and myeloid cell types can vary significantly in a organ‐ and tumor type dependent manner, as suggested by studies employing sophisticated mouse models of cancer engineered to develop in distinctive immunological backgrounds (Andreu et al., 2010; Ciampricotti et al., 2011; Daniel et al., 2005; DeNardo et al., 2009). Such organ‐ and tumor type peculiarities of infiltrating leukocytes may underlay the puzzling controversy surrounding the general prognostic value of macrophage and neutrophil infiltration in human tumors (Azambuja et al., 2011; Qualls and Murray, 2011; Steidl et al., 2011).…”

Infiltrating neutrophils mediate the initial angiogenic switch in a mouse model of multistage carcinogenesis

“…In regard to the innate immune system, despite its capability to stimulate acquired immune responses, the weight of the evidence indicates that infiltration by innate immune cell types is tumorpromoting in many organs and tumorigenesis pathways (1,7,8). In addition to protumorigenic activities of tumor associated macrophages (9-11), neutrophils also have been shown to enhance the in vitro invasive and in vivo metastatic potential of syngeneic tumor cells by facilitating invasion into basement membrane (7).Genetically engineered mouse models of cancer are proving instructive about the immunobiology of tumors, revealing both enhancing and antagonizing roles played by the adaptive and innate immune system (4,5,(12)(13)(14). RIP1-Tag2 transgenic mice constitute a well characterized prototypical model for multistep carcinogenesis, involving the pancreatic islets, which has provided insights into immune interactions during tumorigenesis.…”

“…These stromal cells include cancerassociated fibroblasts, endothelial cells, pericytes, and a variable representation of leukocytes, including macrophages, neutrophils, mast cells, and B or T lymphocytes (1,2). Increasing evidence indicates that leukocytic infiltration can either antagonize tumor formation and growth (immune surveillance) (2,3) or, alternatively, promote tumor phenotypes, such as angiogenesis, growth, and invasion (immune enhancement) (1,4,5). Historically, tumor-infiltrating leukocytes have been considered to be manifestations of an intrinsic defense mechanism against developing tumors (2).…”

“…Genetically engineered mouse models of cancer are proving instructive about the immunobiology of tumors, revealing both enhancing and antagonizing roles played by the adaptive and innate immune system (4,5,(12)(13)(14). RIP1-Tag2 transgenic mice constitute a well characterized prototypical model for multistep carcinogenesis, involving the pancreatic islets, which has provided insights into immune interactions during tumorigenesis.…”