National Cancer Institute team has found a
new chemokine-regulated pathway of tumor immune evasion that could account for
some patients' resistance to checkpoint inhibitor-based therapies.1
By blocking CXC chemokine receptor 2, the team
prevented migration of myeloid-derived suppressor cells and increased the efficacy of programmed cell death 1-targeting mAbs in
a mouse model of rhabdomyosarcoma.
create a system for studying PD-1-independent tumor immune evasion, the team
used a mouse model of rhabdomyosarcoma to establish conditions in which PD-1
inhibition was ineffective. In the model, an anti PD-1 mAb only modestly
decreased tumor growth when given 7 days after tumors were established, whereas
it enabled 100% of the mice to survive when administered at the time of tumor
DuBois told SciBX, "The idea of combining
inhibitors of PD-1 signaling and CXCR2, which target separate immune evasion
mechanisms, is really attractive because there is real potential for
synergistic immunomodulatory activity. Myeloid cells are not involved in the
In addition to combining CXCR2 blockade with adoptive T
cell therapies, DuBois expects that the approach could be combined with many
other cancer therapies.
L. SciBX 7(24); doi:10.1038/scibx.2014.693 Published online June 19, 2014
1. Highfill, S.L. et
al. Sci. Transl. Med.; published online May 21, 2014;
doi:10.1126/scitranslmed.3007974 Contact: Crystal L. Mackall, National
Cancer Institute, National Institutes of Health, Bethesda, Md. e-mail: firstname.lastname@example.org Contact:
Steven L. Highfill, same affiliation as above e-mail: email@example.com
2. McCallister, E. BioCentury
22(23), A1-A7; June 9, 2014
3. Lesokhin, A.M.
et al. Cancer Res. 72, 876-886 (2012)
4. Youn, J.-I. et al.
J. Immunol. 181, 5791-5802 (2008)
B.D. et al. Am. J. Respir. Crit. Care Med. 164, 190-192 (2001)
AND INSTITUTIONS MENTIONED
Arizona State University, Phoenix, Ariz.
(LSE:AZN; NYSE:AZN), London, U.K.
Oss, the Netherlands
Bristol-Myers Squibb Co. (NYSE:BMY), New York, N.Y.
Dompe Farmaceutici S.p.A., Milan, Italy
Mayo Clinic in Arizona, Scottsdale, Ariz.
Merck & Co. Inc. (NYSE:MRK), Whitehouse Station, N.J.
National Cancer Institute, Bethesda, Md.
(SIX:ROG; OTCQX:RHHBY), Basel, Switzerland
Sorrento Therapeutics Inc. (NASDAQ:SRNE), San Diego, Calif.