Deficient tumor-infiltrating T-lymphocyte response in malignant lymphoma: relationship to HLA expression and host immunocompetence.
Tumor-infiltrating T-lymphocytes (T-TIL) are putative mediators of tumor containment that exhibit unique specificity for autologous tumor cells. The magnitude of T-TIL response in biopsy specimens from patients with B-cell lymphoma has been suggested as an independent predictor of clinical outcome. Since recognition of tumor antigens may occur in association with major histocompatibility complex (MHC) molecules, effective T-TIL tumor immunosurveillance may be limited by either failure to express MHC-encoded recognition structures and/or host T-cell immunocompetence. To further delineate T-cell immunoregulation in B-cell lymphoma, we assessed T-TIL fraction and tumor expression of invariant class I and class II HLA determinants by immunohistochemistry in biopsy specimens. Two distinct clinical cohorts of B-cell lymphoma were investigated to delineate pathogenetic differences in T-TIL response. One group, representing immunodeficient and transplant-related lymphomas, comprised 18 patients with AIDS- or allograft-related lymphoma. The second group comprised 83 consecutive cases of sporadic diffuse large cell (DLCL) lymphoma. Median CD8+ T-TIL was significantly lower (4.9% versus 12.7%) among immunodeficiency-associated lymphoma and the frequency of cases with low (< 6%) CD8+ T-TIL greater (76% versus 23%) (p < 0.0001). None of the immunodeficiency-associated lymphomas demonstrated non-polymorphic HLA loss. Absence of one or more class I or II HLA determinants was found in 13 out of 19 (68%) sporadic DLCL specimens with low CD8+ T-TIL, compared to 20% of cases with higher T-TIL fraction (p = 0.0004). These findings implicate impaired host immunosurveillance in deficient T-TIL response in immunodeficiency-associated B-cell lymphoma, whereas low T-TIL in sporadic cases of DLCL relates to tumor loss of HLA determinants. Strategies to modulate tumor HLA expression or augment antitumor response merit investigation in patients with B-cell lymphoma.
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A F
AF
Department of Internal Medicine, University of Arizona College of Medicine, Tucson.
Spier
C M
CM
Miller
T P
TP
Grogan
T M
TM
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016827:CD8 Antigens / Q000276:immunology; D000939:Epitopes / Q000276:immunology; D005260:Female; D006680:HLA Antigens / Q000032:analysis / Q000276:immunology*; D006801:Humans; D007121:Immunocompetence / Q000276:immunology*; D007150:Immunohistochemistry; D007153:Immunologic Deficiency Syndromes / Q000276:immunology* / Q000473:pathology; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D016483:Lymphoma, AIDS-Related / Q000276:immunology* / Q000473:pathology; D016393:Lymphoma, B-Cell / Q000276:immunology / Q000473:pathology; D016403:Lymphoma, Large B-Cell, Diffuse / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D016827:CD8 Antigens; D000939:Epitopes; D006680:HLA Antigens