AUTHOR=Meng Qingda , Valentini Davide , Rao Martin , Maeurer Markus 

TITLE=KRAS RENAISSANCE(S) in Tumor Infiltrating B Cells in Pancreatic Cancer

JOURNAL=Frontiers in Oncology

VOLUME=Volume 8 - 2018

YEAR=2018

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2018.00384

DOI=10.3389/fonc.2018.00384

ISSN=2234-943X

ABSTRACT=KRAS is a driver mutation for malignant transformation, found in 30% of all cancers and in 90% of pancreatic cancer. The identification of small molecules inhibiting selectively KRAS mutants has been challenging, yet mutant KRAS has recently been shown to be targeted by tumor infiltrating T-cells that confer, upon adoptive transfer, tumor regression (Tran, NEJM, 375, 2255, 2016). A human IgG1 monoclonal antibody interfering with mutant KRAS function has been described (Shin, Nat. Comm. 8, 15090, 2017) to inhibit growth of KRAS mutant xenografts. B-cells have been described to infiltrate pancreatic cancer, they may be associated with TLS (tertiary lymphoid structures) associated with good prognosis  - or to promote tumor growth. However, their function, nor their antigen-specificity has been defined. We discuss here the presence of tumor-infiltrating B-cells from patients with pancreatic cancer that produce KRAS-mutant specific IgG. This underlines that intra-tumoral T- and B-cells are able to exclusively target mutant KRAS and that KRAS – specific IgG that could be used as a blueprint for the construction of  tumor-reactive  chimeric antigen receptors (CARs),  even if B-cells may promote tumor growth.