This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Guidoboni, M. Articles by Dolcetti, R. Search for Related Content PubMed PubMed Citation Articles by Guidoboni, M. Articles by Dolcetti, R.

(American Journal of Pathology. 1999;155:823-829.)
© 1999 American Society for Investigative Pathology

Regular Articles

Activation of Infiltrating Cytotoxic T Lymphocytes and Lymphoma Cell Apoptotic Rates in Gastric MALT Lymphomas

Differences between High-Grade and Low-Grade Cases

Massimo Guidoboni^*, Claudio Doglioni, Licia Laurino, Mauro Boiocchi^* and Riccardo Dolcetti^*

From the Division of Experimental Oncology 1,^*
Centro di Riferimento Oncologico, Aviano, Italy; and the Department of Pathology,
Belluno City Hospital, Belluno, Italy

In this study, we have characterized infiltrating T lymphocytes from 13 low-grade and 17 high-grade primary gastric MALT lymphomas by immunohistochemistry, with particular regard to the presence, activation, and topographic distribution of cytotoxic effectors. Although the prevalence of CD4+ and CD8+ cells was similar in low- and high-grade lymphomas, higher numbers of TIA-1+ cytotoxic effectors were found in this latter group of cases (11.6 versus 7.8%; P = 0.004). Activation of CD8+ cytotoxic T lymphocytes (CTLs) was significantly more pronounced in high- than in low-grade lymphomas, as shown by immunostaining for perforin (8.7 versus 4.0%; P = 0.001) and granzyme-B (GrB) (8.7% versus 3.0%; P < 0.0001). Of note, CD20/GrB double labeling showed that high-grade lymphomas carried a markedly higher content (about ninefold) of activated CTLs relative to the number of CD20+ lymphoma B cells (0.081 ± 0.076 versus 0.009 ± 0.011; P < 0.0001). Moreover, high-grade lymphomas showed significantly increased apoptotic rates compared to low-grade cases (5.3 and 1.1% of terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-positive cells, respectively; P < 0.0001). In the whole series, the percentage of GrB+ cells and the GrB+/CD20+ ratio showed a strong linear correlation with the number of TUNEL-labeled cells. These findings, together with the frequent colocalization of CTLs and TUNEL+ neoplastic cells, suggested that apoptotic death of lymphoma cells may be due at least in part to the killing by cytotoxic effectors. Our results are consistent with the occurrence of host antitumor cell-mediated immune responses in gastric MALT lymphomas. Moreover, the finding of stronger cytotoxic responses in high- than in low-grade cases is of potential usefulness in the design of more effective therapeutic strategies for the management of these disorders.

This article has been cited by other articles:

				T. Ishikawa, T. Fujita, Y. Suzuki, S. Okabe, Y. Yuasa, T. Iwai, and Y. Kawakami Tumor-specific Immunological Recognition of Frameshift-mutated Peptides in Colon Cancer with Microsatellite Instability Cancer Res., September 1, 2003; 63(17): 5564 - 5572. [Abstract] [Full Text] [PDF]

				A. Morgner, S. Miehlke, W. Fischbach, W. Schmitt, H. Muller-Hermelink, A. Greiner, C. Thiede, J. Schetelig, A. Neubauer, M. Stolte, et al. Complete Remission of Primary High-Grade B-Cell Gastric Lymphoma After Cure of Helicobacter pylori Infection J. Clin. Oncol., April 1, 2001; 19(7): 2041 - 2048. [Abstract] [Full Text] [PDF]