Loss of B7.2 (CD86) and intracellular adhesion molecule 1 (CD54) expression is associated with decreased tumor-infiltrating T lymphocytes in diffuse B-cell large-cell lymphoma
At. Stopeck et al., Loss of B7.2 (CD86) and intracellular adhesion molecule 1 (CD54) expression is associated with decreased tumor-infiltrating T lymphocytes in diffuse B-cell large-cell lymphoma, CLIN CANC R, 6(10), 2000, pp. 3904-3909
Tumor-infiltrating CD8+ T-lymphocytes (T-TILs) are thought to be relevant t
o immunosurveillance of several tumor types including B-cell non-Hodgkin's
lymphoma. B- and T-lymphocyte interactions via cellular adhesion molecules
(CAMs), recognition molecules (HLAs), and costimulatory molecules (CSMs) ar
e necessary for optimal antigen-specific T-cell activation to occur and may
be important in generating effective host T-TIL responses. me previously f
ound that low T-TIL response (CD8+ T cells < 6%) correlates with statistica
lly shorter relapse-free survival in patients,vith diffuse large-cell lymph
oma (DLCL), We now extend our observations in 71 DLCL patients by analyzing
malignant B-cell expression of the following molecules important in T-cell
activation: (a) recognition molecules [MHC I (MAS and MCA) and MHC (HLA-DR
, -DP, -DQ)]; (b) CAMs [leukocyte function antigen 1 (CD11a and CD18) and i
ntracellular adhesion molecule (CD54)]; and (c) CSMs [B7.1 (CD80) and B7.2
(CD86)]. Eighteen patients (25%) had low a T-TIL response, and 53 patients
(75%) had a high T-TIL response. Overall, expression of the MHC class II mo
lecules BLA-DR and HLA-DQ was most conserved. The loss of B7.2 (P = 0.04),
intracellular adhesion molecule 1 (P = 0.0004), MAS (P = 0.02), and HLA-DR
(P = 0.0004) expression was significantly associated with decreased T-TIL r
esponse. In 100% of patients with low T-TIL responses, at least one BLA, CA
M, or CSM was undetectable on the malignant B cells by immunohistochemical
staining (mean number of molecules lost = 2.67), In contrast, 49% of patien
ts with high T-TIL responses had no losses in HLA, CAM, or CSM expression (
mean number of molecules lost = 0.89), The mean number of absent molecules
(HLA, CAM, or CSM) was significantly associated with T-TIL response (P = 0.
0001). We conclude that loss of HLA, CAM, or CSM expression on malignant B
cells is associated with a poor host T-cell immune response, In addition, b
ecause patients with low T-TIL response had lost expression of multiple cel
lular adhesion, recognition, and costimulatory molecules, our results sugge
st that a combination of immunorestorative therapies may be required to gen
erate effective antitumor T-cell responses in B-cell DLCL.