Functional down-regulation of beta 1 and beta 2 integrins on lamina propria lymphocytes (LPL) and tumor-infiltrating lymphocytes (TIL) in colorectal cancer patients

Integrins play an important role in various lymphocyte functions. In this s tudy, we isolated lamina propria lymphocytes (LPL) and tumor-infiltrating l ymphocytes (Tn) from normal and malignant tissues in patients with colorect al cancer, and examined the expression of beta 1 and beta 2 integrins on th ese lymphocytes quantitatively with two-color flow cytometry, Both LPL and Tn expressed a lower level of common beta 1 chain (CD29) in CD4 and CD8 sub populations than did peripheral blood lymphocytes (PBL). Among the associat ed alpha chains, the expression levels of alpha 1 (CD49a) and alpha 2 (CD49 b) were slightly higher, whereas those of alpha 4 (CD49d) and alpha 6 (CD49 f) were markedly reduced in LPL and Tn. No significant differences were obs erved in expressions of any beta 1 integrin chains between these two lympho cytes populations. Similarly, both alpha L (CD11a) and beta 2 (CD18) were d own-regulated in TIL and LPL with CD8(+) cytotoxic phenotype, but not in th ese with CD4 phenotype. CD8(+) TIL expressed a slightly but significantly h igher level of alpha L beta 2 than did CD8 LPL. CD8(+) LPL and CD8(+) TIL c onsistently 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 di d CD8(+) LPL, the level was much lower than that in PBL. The expression pat tern and functional down-regulation of these integrins may be one of the re asons why TIL cannot eradicate the cancer cells in colorectal cancer.