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=8 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. It is found in 30% of all cancers and in 90% of pancreatic cancers. The identification of small molecules selectively inhibiting KRAS mutants has been challenging, yet mutant KRAS has recently been shown to be targeted by tumor-infiltrating lymphocyte (TIL)-derived T cells that confer tumor regression upon adoptive transfer. Furthermore, a human IgG1 monoclonal antibody interfering with mutant KRAS function inside the cell has been described to inhibit growth of KRAS-mutant xenografts in tumor-bearing mice. B cells have been described to infiltrate pancreatic cancer and may be associated with tertiary lymphoid structures associated with good prognosis, or, in contrast, promote tumor growth. However, their function, nor their antigen-specificity has been clearly defined. We discuss here the presence of tumor-infiltrating B cells (TIB) in patients with pancreatic cancer that produce KRAS-mutant specific IgG, underlining that intratumoral T and B cells may exclusively target mutant KRAS. KRAS-specific IgG may, therefore, serve as a readout of the activation of both arms of the anti-tumor adaptive immune armament although some B-cell populations may promote tumor progression.