Functional down-regulation of beta1 and beta2 integrins of lamina propria lymphocytes (LPL) and tumor-infiltrating lymphocytes (TIL) in colorectal cancer patients

Abstract

Integrins play an important role in various lymphocyte functions. In this study, we isolated lamina propria lymphocytes (LPL) and tumor-infiltrating lymphocytes (TIL) from normal and malignant tissues in patients with colorectal cancer, and examined the expression of beta1 and beta2 integrins on these lymphocytes quantitatively with two-color flow cytometry. Both LPL and TIL expressed a lower level of common beta1 chain (CD29) in CD4 and CD8 subpopulations than did peripheral blood lymphocytes (PBL). Among the associated alpha chains, the expression levels of alpha1 (CD49a) and alpha2 (CD49b) were slightly higher, whereas those of alpha4 (CD49d) and alpha6 (CD49f) were markedly reduced in LPL and TIL. No significant differences were observed in expressions of any alpha1 integrin chains between these two lymphocytes populations. Similarly, both alphaL (CD11a) and beta2 (CD18) were down-regulated in TIL and LPL with CD8+ cytotoxic phenotype, but not in those with CD4+ phenotype. CD8+ TIL expressed a slightly but significantly higher level of alphaLbeta2 than did CD8+ LPL. CD8+ LPL and CD8+ TIL consistently showed significantly decreased binding to purified ICAM-1, VCAM-1 and HT29 colon cancer cells as compared with CD8+ PBL. Although CD8+ TIL showed a slightly higher level of adhesion to these substrates than did CD8+ LPL, the level was much lower than that in PBL. The expression pattern and functional down-regulation of these integrins may be one of the reasons why TIL cannot eradicate the cancer cells in colorectal cancer.