Deficient tumor-infiltrating T-lymphocyte response in malignant lymphoma

Relationship to HLA expression and host immunocompetence

Alan F. List, Catherine S Perry, Thomas P Miller, Thomas M. Grogan

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

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 histocompatability 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 Il 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 CDS+ 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.

Original languageEnglish (US)
Pages (from-to)398-403
Number of pages6
JournalLeukemia
Volume7
Issue number3
StatePublished - Mar 1993

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Tumor-Infiltrating Lymphocytes
Immunocompetence
Lymphoma
T-Lymphocytes
B-Cell Lymphoma
Immunologic Monitoring
Neoplasms
Biopsy
Lymphoma, Large B-Cell, Diffuse
Lymphokines
Neoplasm Antigens
Allografts

ASJC Scopus subject areas

  • Cancer Research
  • Hematology

Cite this

Deficient tumor-infiltrating T-lymphocyte response in malignant lymphoma : Relationship to HLA expression and host immunocompetence. / List, Alan F.; Perry, Catherine S; Miller, Thomas P; Grogan, Thomas M.

In: Leukemia, Vol. 7, No. 3, 03.1993, p. 398-403.

Research output: Contribution to journalArticle

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abstract = "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 histocompatability 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 Il 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 CDS+ 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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