In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 72, No. 8_Supplement ( 2012-04-15), p. 4391-4391
Kurzfassung:
Using the K14-HPV16 mouse model of squamous carcinogenesis (SCC), we previously reported that B cells foster neoplastic progression through deposition of immunoglobulin complexes in premalignant tissue via Fcα receptor-dependent activation of recruited myeloid cells. Here we evaluated therapeutic interventions targeting these pathways in preclinical trials through administration of depleting αCD20 antibody and small molecule inhibitor of Syk kinase. Both approaches harbored efficacy in preventing premalignant progression to the dysplastic/carcinoma in situ state. Screening a diverse spectrum of human solid tumors revealed SCCs of the vulva, head and neck, as well as pancreatic ductal adenocarcinomas (PDAC) as scoring positively for “signatures” of B cell or plasma cell infiltration, i.e. Ig or CD20 mRNA expression, thereby identifying carcinomas potentially amenable to anti-B cell therapies. Accordingly, B cell-deficient mice failed to support growth of either transplantable orthotopic SCC or PDAC. While administration of αCD20 mAB as a single agent was inefficient in impeding growth of preexisting SCCs, when delivered in combination with cytotoxic chemotherapy, e.g., paclitaxel, carboplatin or cisplatin, αCD20 mAb significantly improved chemotherapeutic response and improved survival by a mechanism dependent on CD8+ T cells. These data reveal that blocking protumorigenic programs regulating by humoral immunity, in combination with chemotherapy, effectively reprograms the tumor immune microenvironment and improves outcome. The authors acknowledge generous support from the NIH/NCI (R01CA130980, R01CA13256, R01CA140943, R01CA15531), the Department of Defense (W81XWH-09-1-0342, W81XWH-10-BCRP-EOHS-EXP) and the Susan G Komen Foundation (KG111084) Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4391. doi:1538-7445.AM2012-4391
Materialart:
Online-Ressource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2012-4391
Sprache:
Englisch
Verlag:
American Association for Cancer Research (AACR)
Publikationsdatum:
2012
ZDB Id:
2036785-5
ZDB Id:
1432-1
ZDB Id:
410466-3
Permalink
