PMID- 10487840 OWN - NLM STAT- MEDLINE DCOM- 19991007 LR - 20181113 IS - 0002-9440 (Print) IS - 1525-2191 (Electronic) IS - 0002-9440 (Linking) VI - 155 IP - 3 DP - 1999 Sep TI - Activation of infiltrating cytotoxic T lymphocytes and lymphoma cell apoptotic rates in gastric MALT lymphomas. Differences between high-grade and low-grade cases. PG - 823-9 AB - 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. FAU - Guidoboni, M AU - Guidoboni M AD - Division of Experimental Oncology 1,(*) Centro di Riferimento Oncologico, Aviano, Italy Belluno City Hospital, Belluno, Italy. FAU - Doglioni, C AU - Doglioni C FAU - Laurino, L AU - Laurino L FAU - Boiocchi, M AU - Boiocchi M FAU - Dolcetti, R AU - Dolcetti R LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Am J Pathol JT - The American journal of pathology JID - 0370502 RN - 0 (Antigens, CD20) RN - 0 (CD56 Antigen) RN - 0 (GRB10 protein, human) RN - 0 (Membrane Proteins) RN - 0 (Poly(A)-Binding Proteins) RN - 0 (Proteins) RN - 0 (RNA-Binding Proteins) RN - 0 (T-Cell Intracellular Antigen-1) RN - 0 (TIA1 protein, human) RN - 151441-47-3 (GRB10 Adaptor Protein) SB - IM MH - Antigens, CD20/metabolism MH - *Apoptosis MH - CD4-CD8 Ratio MH - CD56 Antigen/metabolism MH - Cell Count MH - GRB10 Adaptor Protein MH - Humans MH - Immunohistochemistry MH - In Situ Nick-End Labeling MH - Lymphocyte Activation/*immunology MH - Lymphocytes, Tumor-Infiltrating/immunology/*metabolism MH - Lymphoma, B-Cell, Marginal Zone/*immunology/pathology MH - Membrane Proteins/metabolism MH - Poly(A)-Binding Proteins MH - Proteins/metabolism MH - RNA-Binding Proteins/metabolism MH - Stomach Neoplasms/*immunology/pathology MH - T-Cell Intracellular Antigen-1 MH - T-Lymphocytes, Cytotoxic/immunology/*metabolism PMC - PMC1866896 EDAT- 1999/09/17 00:00 MHDA- 1999/09/17 00:01 PMCR- 2000/03/01 CRDT- 1999/09/17 00:00 PHST- 1999/09/17 00:00 [pubmed] PHST- 1999/09/17 00:01 [medline] PHST- 1999/09/17 00:00 [entrez] PHST- 2000/03/01 00:00 [pmc-release] AID - S0002-9440(10)65181-4 [pii] AID - 1866 [pii] AID - 10.1016/S0002-9440(10)65181-4 [doi] PST - ppublish SO - Am J Pathol. 1999 Sep;155(3):823-9. doi: 10.1016/S0002-9440(10)65181-4.