PMID:24083082

Citation	Guirnalda, P, Wood, L, Goenka, R, Crespo, J and Paterson, Y (2013) Interferon γ-induced intratumoral expression of CXCL9 alters the local distribution of T cells following immunotherapy with Listeria monocytogenes. Oncoimmunology 2:e25752
Abstract	The ability of Listeria monocytogenes-based anticancer vaccines to induce tumor regression depends on the responsiveness of malignant cells to interferon γ (IFNγ). Inhibition of IFNγ limits the recruitment of T cells to the tumors of vaccinated mice. We hypothesized that vaccination with immunotherapeutic L. monocytogenes induces the IFNγ-dependent production of chemokines that regulate the migration of tumor-infiltrating T cells. To gain further insights into this issue, we examined the chemokine responses of a transplantable, human papillomavirus (HPV)-immortalized murine tumor model (TC-1) following the administration of a L. monocytogenes-based immunotherapeutic agent that expresses E7 from HPV-16. Here, we report that the administration of L. monocytogenes-based anticancer vaccines increases the secretion of chemokine (C-X-C motif) ligand 9 (CXCL9), and CXCL10 by tumors, hence favoring the recruitment of T cells bearing the cognate chemokine (C-X-C motif) receptor 3 (CXCR3). Furthermore, the expression of CXCL9, but not CXCL10, in TC-1 tumors was significantly reduced upon anti-IFNγ antibody treatment. CXCL9 was highly expressed by TC-1 cells following the administration of IFNγ and tumor necrosis factor α (TNFα), in vitro. Moreover, the inhibition of CXCL9 in TC-1 cells reduced the proportion of CD8(+) T cells infiltrating tumors in vaccinated mice, while increasing that of CD4(+) T cells, thus altering T-cell subset distribution. We conclude that the administration of L. monocytogenes-based anticancer vaccines regulates TH1 chemokine responses and that malignant cells are an important source of these chemokines.
Links	PubMed PMC3782529 Online version:10.4161/onci.25752
Keywords
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
MOUSE:CXCL9		GO:0006935: chemotaxis	ECO:0000314:		P		Figure 5 illustrates the effect of CXCL9 knockout influences the distribution of Tcell subsets in mice.	complete CACAO 8780

References

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