Murine splenic CD4⁺ T cells, induced by innate immune cell interactions and secreted factors, develop antileukemia cytotoxicity.

Abstract:

:Inciting the cellular arm of adaptive immunity has been the fundamental goal of cancer immunotherapy strategies, specifically focusing on inducing tumor antigen-specific responses by CD8(+) cytotoxic T lymphocytes (CTL). However, there is an emerging appreciation that the cytotoxic function of CD4(+) T cells can be effective in a clinical setting. Harnessing this potential will require an understanding of how such cells arise. In this study, we use an IL12-transduced variant of the 70Z/3 leukemia cell line in a B6D2F1 (BDF1) murine model system to reveal a novel cascade of cells and soluble factors that activate anticancer CD4(+) killer cells. We show that natural killer T cells play a pivotal role by activating dendritic cells in a contact-dependent manner; soluble products of this interaction, including MCP-1, propagate the activation signal, culminating in the development of CD4(+) CTLs that directly mediate an antileukemia response while also orchestrating a multipronged attack by other effector cells. A more complete picture of the conditions that induce such a robust response will allow us to capitalize on CD4(+) T-cell plasticity for maximum therapeutic effect.

journal_name

Cancer Immunol Res

authors

Nelles ME,Moreau JM,Furlonger CL,Berger A,Medin JA,Paige CJ

doi

10.1158/2326-6066.CIR-13-0208

subject

Has Abstract

pub_date

2014-11-01 00:00:00

pages

1113-24

issue

11

eissn

2326-6066

issn

2326-6074

pii

2326-6066.CIR-13-0208

journal_volume

2

pub_type

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