Assessing Cd8 T Cell Number and Dysfunction in the Presence of Antigen

Rapid recovery of CD4+ T cells after intensive chemotherapy is limited by an age-dependent decline in thymopoiesis. Here we sought to determine whether similar limitations exist for CD8+ T-cell regeneration. After intensive chemotherapy, CD8+ T cells had a faster effective doubling time than CD4+ T cells (median, 12.6 v 28.2 days, P < .05). Accordingly, at 3 months posttherapy, mean CD8+ T-cell number had returned to baseline, whereas mean CD4+ T-cell number was only 35% of pretherapy values (P < .05). These differences were primarily due to very rapid expansion of CD8+CD57+ and CD8+CD28− subsets. At 3 months posttherapy, there was no relationship between age and CD8+ T-cell number (R = −.02), whereas CD4+ T-cell number was inversely related to age (R = −.66) and there were no discernible differences in CD8+ recovery among patients with or without thymic enlargement, whereas CD4+ recovery was enhanced in patients with thymic enlargement after chemotherapy (P < .01). Therefore thymic-independent pathways of T-cell regeneration appear to rapidly regenerate substantial numbers of CD8+, but not CD4+ T cells, resulting in prolonged T-cell subset imbalance after T-cell depletion. These inherent distinctions between CD4+v CD8+ T-cell regeneration may have significant implications for immunotherapeutic strategies undertaken to eradicate minimal residual neoplastic disease after cytoreductive chemotherapy.

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Prognostic Implications of Infiltrating T Cells Within Tumors for Patients With Esophageal Squamous Cell Carcinoma: A Retrospective Cohort Study

10.21203/rs.3.rs-46066/v1 ◽

2020 ◽

Author(s):

Peng Yang ◽

Pan Xiong ◽

Yuanning Guo ◽

Haihua Huang ◽

Shaobin Chen ◽

...

Keyword(s):

Overall Survival ◽

Squamous Cell Carcinoma ◽

T Cells ◽

T Cell ◽

Esophageal Squamous Cell Carcinoma ◽

Cd8 T Cells ◽

Cd8 T Cell ◽

Cell Number ◽

T Cell Infiltration ◽

Prognostic Implications

Abstract Background: Infiltrating T lymphocytes within tumors have been recognized to be associated with patient survival in various cancer types. For esophageal squamous cell carcinoma (ESCC), the prognostic implications of infiltrating CD3+ and CD8+ T cells have yet to be validated in more extensive patient groups.Methods: We evaluated the numbers of infiltrating CD3+ and CD8+ T cells within tumors from 461 patients with ESCC using immunohistochemistry and analyzed its impacts on overall survival.Results: The median number of infiltrating CD3+ and CD8+ T cell per field was 16.0 (P25-P75: 9.2-28.6) and 8.0 (3.8-20.2), respectively, with obvious correlation between them (rs = 0.65, p < 0.0001). Age and tumor grade were associated with the numbers of infiltrating T cells (all p < 0.05). A high number of infiltrating CD3+ T cells was associated with prolonged overall survival (unadjusted HR for high vs low: 0.73, 95% CI: 0.55-0.98), whereas CD8+ T cell number was not (0.90, 0.68-1.20). Multivariate Cox analysis identified that T stage, lymph node metastasis, and infiltrating CD3+ T cell number were independent prognostic factors (all p < 0.05).Conclusions: Our results indicate that CD3+ T cell infiltration within tumors is an independent prognostic factor for ESCC patients, whereas CD8+ T cell infiltration has no prognostic implications.

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Distinctions Between CD8+ and CD4+ T-Cell Regenerative Pathways Result in Prolonged T-Cell Subset Imbalance After Intensive Chemotherapy

Blood ◽

10.1182/blood.v89.10.3700 ◽

1997 ◽

Vol 89 (10) ◽

pp. 3700-3707 ◽

Cited By ~ 268

Author(s):

Crystal L. Mackall ◽

Thomas A. Fleisher ◽

Margaret R. Brown ◽

Mary P. Andrich ◽

Clara C. Chen ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Cd4 T Cells ◽

Cell Subset ◽

Cd8 T Cell ◽

Cell Number ◽

Cd4 T Cell ◽

Cell Regeneration ◽

Intensive Chemotherapy ◽

T Cell Subset

Abstract Rapid recovery of CD4+ T cells after intensive chemotherapy is limited by an age-dependent decline in thymopoiesis. Here we sought to determine whether similar limitations exist for CD8+ T-cell regeneration. After intensive chemotherapy, CD8+ T cells had a faster effective doubling time than CD4+ T cells (median, 12.6 v 28.2 days, P < .05). Accordingly, at 3 months posttherapy, mean CD8+ T-cell number had returned to baseline, whereas mean CD4+ T-cell number was only 35% of pretherapy values (P < .05). These differences were primarily due to very rapid expansion of CD8+CD57+ and CD8+CD28− subsets. At 3 months posttherapy, there was no relationship between age and CD8+ T-cell number (R = −.02), whereas CD4+ T-cell number was inversely related to age (R = −.66) and there were no discernible differences in CD8+ recovery among patients with or without thymic enlargement, whereas CD4+ recovery was enhanced in patients with thymic enlargement after chemotherapy (P < .01). Therefore thymic-independent pathways of T-cell regeneration appear to rapidly regenerate substantial numbers of CD8+, but not CD4+ T cells, resulting in prolonged T-cell subset imbalance after T-cell depletion. These inherent distinctions between CD4+v CD8+ T-cell regeneration may have significant implications for immunotherapeutic strategies undertaken to eradicate minimal residual neoplastic disease after cytoreductive chemotherapy.

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