Major histocompatibility antigens and antigen‐processing molecules in retinoblastoma

Abstract

BACKGROUNDMalignant transformation of cells is frequently associated with abnormalities in human leukocyte antigen (HLA) expression. These abnormalities may play a role in the clinical course of the disease, because HLAs mediate interactions of tumor cells with cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells. Retinoblastoma is the most common intraocular malignant tumor in childhood and is characterized by direct spread to the optic nerve and orbit as well as hematogeneous and lymphatic spread. Little is known about the role of HLA expression in the progression of this malignant disease.METHODSHLA Class I antigen, β2‐microglobulin (β2‐m), HLA Class II antigens, and the antigen‐processing molecules (APMs) of the HLA Class I pathway, including proteasomal subunits (low–molecular mass polypeptide 2 [LMP‐2] and LMP‐10), the transporter‐associated protein (TAP‐1) subunit, the binding protein tapasin, and the chaperone molecule calnexin, were studied in 30 archival retinoblastoma specimens by immunohistochemistry. Immunoanalysis was performed based on the International Histocompatibility Working Group Project Description.RESULTSHLA Class I antigen, β2‐m, HLA Class II antigen, and APMs were positive in 12 tumors with no invasion and were decreased in 13 tumors with choroidal and optic nerve invasion. The difference in HLA and APM expression between the 2 groups was statistically significant (P < 0.001).CONCLUSIONSDecreased expression of HLA was observed in aggressive tumors and in poorly differentiated tumors. The current findings support a role for both CTLs and NK cell‐mediated control of tumor growth in the clinical course of retinoblastoma. Cancer 2004;100:1059–69. © 2004 American Cancer Society.

Clinical significance of HLA class I heavy chain expression in patients with gastric cancer

“…These studies suggested that downregulation of HLA-I (i.e., mixed or negative HLA-I expression) might reflect the escape of malignant cells from human immune system. On the other hand, other studies reported that cancers with downregulated HLA-I were correlated with early tumor stage and better prognosis including breast cancer [9], uveal melanoma [12], non-small cell lung cancer [14], and colorectal cancer [17]. These results reflect the controversy about the exact role of HLA-I expression in malignancies.…”

“…In recent years, reduced or loss of HLA-I expression has been reported to be associated with tumor development or patients' outcome in breast cancer [8][9][10], malignant melanoma [11,12], laryngeal carcinoma [13], small cell carcinoma of the lung [14], ovary carcinoma [15], cervical carcinoma [16], and colorectal cancer [17]. However, the relation of HLA-I, especially heavy chain of HLA-I, expression with patients' outcome in gastric cancer has not yet been investigated.…”

Loss of tapasin in human lung and colon cancer cells and escape from tumor-associated antigen-specific CTL recognition

“…8,9 Loss of tapasin expression is a frequent event that has been reported in a wide variety of human cancers, including malignant melanoma, head and neck squamous cell carcinoma (HNSCC), renal cell carcinoma, colorectal carcinoma, glioblastoma, lung carcinoma, and neuroblastoma. [10][11][12][13][14][15][16][17][18] Notably, tapasin expression associated with intratumoral T-cell infiltration has been reported as a prognostic marker of patient survival in ovarian carcinoma, HNSCC, glioblastoma, and colorectal carcinoma. 12,13,[19][20][21] It is also reported that loss of tapasin is more frequent among the other antigen-processing machinery (APM) components, strongly suggesting its central role in escape from CTL immune surveillance to tumors.…”

TAP genes and immunity

“…Coordinated loss of all the components of the PLC and other gene products involved in antigen presentation occurs in retinoblastoma [91], colorectal carcinoma [92] and in a mouse model of metastatic fibrosarcoma [93].…”