Immune reconstitution from peripheral blood mononuclear cells inhibits lung carcinoma growth in NOD/SCID mice

Abstract

Drug resistance and immune deficiency are important factors for the poor prognosis of lung carcinoma. The present study explored the possible protective effect of immune reconstitution from peripheral blood mononuclear cells (PBMCs) on multi-drug-resistant human lung carcinoma Am1010 cells in non-obese diabetic/severe combined immunodeficient (NOD/SCID) mice. The inoculated tumor fragments grew rapidly in the NOD/SCID mice. The growth was significantly inhibited by intraperitoneal injection of PBMCs. In the mice injected with PBMCs, numerous CD3⁺ and CD8⁺ cells, but less CD4⁺ cells, were found in spleen and tumor tissues. These data suggest that PBMC transplantation inhibits lung carcinoma progression via the reconstitution of the immune system, particularly of cytotoxic T lymphocytes.

Keywords: Am1010; NOD/SCID; T lymphocytes; lung carcinoma; peripheral blood mononuclear cells.

Figure 1

Tumor growth was observed after tumor segments were inoculated into the SCID/NOD mice, which were injected intraperitoneally human PBMCs or not. (A) The tumor growth curve by palpation, (B) tumors at the fourth week after inoculation, (C) the tumor area by fluorescence imaging and (D) tumor fluorescence imaging after inoculation. ^*P<0.05, vs. the AM1010+PBMC group. SCID/NOD, non-obese diabetic/severe combined immunodeficient; PBMCs, peripheral blood mononuclear cells.

Figure 2

T lymphocytes in the peripheral blood. T-lymphocyte marker CD3 was measured with flow cytometry in PBMC-injected mice of the PBMC and AM1010+PBMC groups. The percentages of CD3⁺ cells among total nucleated cells are shown. SCID/NOD, non-obese diabetic/severe combined immunodeficient; PBMCs, peripheral blood mononuclear cells.

Figure 3

Recruitment of T lymphocytes in the spleen. The spleens were removed after four weeks of tumor segment inoculation and/or PBMC injection. The positive cells and expression levels of CD3, CD4, CD8 and FoxP3 were examined by (A) immunohistochemistry (magnification, ×200) and (B) western blotting. The gray value was shown. ^*P<0.05, vs. the AM1010+PBMC group. PBMC, peripheral blood mononuclear cell.

Figure 4

Recruitment of T lymphocytes in tumors. The tumors were removed after four weeks of tumor segment inoculation. (A) The tumor infiltrating cells were tested with hematoxylin and eosin staining (magnification, ×200). The positive cells and expression levels of CD3, CD4, CD8 and FoxP3 were examined by (B) immunohistochemistry (magnification, ×200) and (C) western blotting. PBMC, peripheral blood mononuclear cell.