Lymphotactin Expression by Engineered Myeloma Cells Drives Tumor Regression: Mediation by CD4+ and CD8+ T Cells and Neutrophils Expressing XCR1 Receptor

Abstract

The C chemokine lymphotactin has been characterized as a T cell chemoattractant both in vitro and in vivo. To determine whether lymphotactin expression within tumors could influence tumor growth, we transfected an expression vector for lymphotactin into SP2/0 myeloma cells and tested their ability to form tumors in BALB/c and nude mice. Transfection did not alter cell growth in vitro. Whereas SP2/0 cells gave rise to a 100% tumor incidence, lymphotactin-expressing SP2/0-Lptn tumors invariably regressed in BALB/c mice and became infiltrated with CD4+ and CD8+ T cells and neutrophils. Regression of the SP2/0-Lptn tumors was associated with a type 1 cytokine response and dependent on both CD4+ and CD8+ T cells, but not NK cells. Both SP2/0 and SP2/0-Lptn tumors grew in nude mice, but growth of the latter tumors was retarded and associated with heavy neutrophil responses; this retardation of SP2/0-Lptn tumor growth was reversed by neutrophil depletion of the mice. Our data also indicate that mouse neutrophils express the lymphotactin receptor XCR1 and that lymphotactin specifically chemoattracts these cells in vitro. Thus, lymphotactin has natural adjuvant activities that may augment antitumor responses via effects on both T cells and neutrophils and thereby could be important in gene transfer immunotherapies for some cancers.

Intratumoral coinjection of two adenoviral vectors expressing functional interleukin-18 and inducible protein-10, respectively, synergizes to facilitate regression of established tumors

“…T-cell subset depletion experiments were performed in vivo as described. 19 Briefly, BALB /c mice (eight per group ) were i.p. injected with anti-CD4 and anti -CD8 antibodies, respectively, at 0.5 mg per mouse 2 days before, on the day of and 3 and 6 days subsequent to the intratumoral injection of adenovirus.…”

Lymphotactin cotransfection enhances the therapeutic efficacy of dendritic cells genetically modified with melanoma antigen gp100

“…Lptn and RANTES gene transfer could generate antitumor immunity and inhibit the tumor growth. 33,34 IP-10 and MIG are potent chemoattractants for Th1 and induce T lymphocytes to the tumor site and result in tumor regression. 35 Injection of adenovirus-mediated encoding MIP-3␣ into subcutaneous tumors induced the local accumulation of DC and elicited tumor-specific CTL activity, and significantly inhibited growth of established tumors.…”

Production of biologically active human lymphotactin (XCL1) by Lactococcus lactis

“…and CD8? cells and neutrophils expressing the XCR1 receptor, the receptor for LTN (Cairns et al 2001). Another approach to use LTN as an enhancer of immune responses was with the manipulation of dendritic cells (DCs) for the expression of this chemokine.…”