Tumor-Infiltrating B-Cell-Derived IgG Recognizes Tumor Components in Human Lung Cancer

Abstract

Tumor-infiltrating lymphocytes consist predominantly of T cells, whereas B cells, plasma cells, and natural killer cells are observed with different degrees of frequency. We investigated the nature of tumor-infiltrating B lymphocytes (TIB) in human lung cancer. First, to examine the ability of immunogloblin production by TIB, cancer tissues were subcutaneously transplanted in severe combined immunodeficient mice, and the murine serum was examined for the concentration of human immunogloblin. Human IgG (huIgG) was detected in the serum of all 12 mice engrafted with lung cancer tissues. huIgM was almost undetectable. The levels of huIgG reached a peak approximately 6 weeks after engraftment and gradually decreased but were detectable until 20 weeks postengrafment. Serum from a large cell carcinoma-engrafted mouse reacted with a protein of 60 kDa derived from lung cancer cell lines (PC-9, Sq-1) and autologous tumor cells but did not react with cell lysates of normal lung tissue. Serum from an adenocarcinoma-engrafted mouse reacted with two proteins, 33 and 55 kDa, derived from lung cancer cell lines (PC-9, Sq-1, A549) and autologous tumor cells but did not react with the lysate of normal lung tissues. These results suggest that B cells infiltrating lung cancer tissues produce IgG that recognizes common tumor-specific antigen.

Identification of tumor associated antigens recognized by IgG from tumor‐infiltrating B cells of lung cancer: Correlation between Ab titer of the patient's sera and the clinical course

“…(28)(29)(30)(31) We focused our attention on the role of TIB in the tumor-specific immune response. In a previous study, (24) we showed that TIB produce IgG in SCID mice when lung cancer tissue is xenotransplanted. Furthermore, we applied the TIB-derived IgG to the SEREX method and identified 37 antigens in a patient with lung cancer (A904).…”

“…We found that human IgG was produced by TIB in the serum of SCID mice, and western blot analysis revealed that such human IgG could react with the proteins from tumor lysates. ( 24 ) Williams et al. also reported that the serum from tumor‐engrafted SCID mice could react with the high and low molecular weight proteins derived from both the membrane and cytosolic fractions of tumor cell lysates.…”

“…We found that human IgG was produced by TIB in the serum of SCID mice, and western blot analysis revealed that such human IgG could react with the proteins from tumor lysates. (24) Williams et al also reported that the serum from tumor-engrafted SCID mice could react with the high and low molecular weight proteins derived from both the membrane and cytosolic fractions of tumor cell lysates. (25) In the present study, we identified the tumor antigens in the pleomorphic carcinoma of the lung by using IgG produced by TIB, and we also demonstrated serial changes in the humoral immune response against them in relation to the clinical course of the patient.…”

SCID mouse models to study human cancer pathogenesis and approaches to therapy: potential, limitations, and future directions

“…The surgical implantation of non-disrupted human lung tumor tissue ( Figure 1) revealed the following: (1) Successful engraftment of hu-TIL occurs in more than 95% of patient tumors xenografted, regardless of the histological type of tumor (63); (2) Human TIL remain at the site of the xenograft and show evidence of proliferation in situ (63); (3) The huIg present in the SCID mouse sera is primarily IgG (167) and is produced by human plasma cells in T-cell dependent manner (63); (4) Sera from xenografted mice contain antibodies that react against proteins derived from autologous tumor tissue (63,167), as well as allogeneic lung tumor cell-lines (167), but not normal lung tissue (167); (5) High levels of huIg in the sera of mice engrafted with tumor biopsy tissue are associated with the growth arrest of adenocarcinoma xenografts (63); and (6) Serial passage of lung tumor Data obtained from gene array analysis of human lung tumor xenografts following treatment in vivo. Xenografts were established s.c. in SCID mice from a patient lung tumor biopsy specimen, and treated one week later by direct intra-tumoral injection of biodegradable microspheres loaded with recombinant human IL-12, or control (cytokine-free) BSA-loaded microspheres.…”

Malignant mesothelioma‐associated antigens recognized by tumor‐infiltrating B cells and the clinical significance of the antibody titers

“…Previous studies demonstrated that TIB produce IgG in SCID mice xenotransplanted with human lung cancer tissue. (10)(11)(12)(13)20) TIB-derived IgG was analyzed by the SEREX method and 22 antigens were identified in a patient with lung cancer. A mutated p53 was one of the identified antigens and the change in the antibody titer against mutated p53 was correlated with the clinical course of the patient.…”