Prognostic effects of PD-1 expression in tumor-infiltrating T cells in patients with B-cell lymphoma in nonimmunotherapy settings
| Reference . | Lymphoma (No. of patients with follow-up) . | Antibody (manufacturer or source) . | PD-1+/high cutoff . | Prevalence of PD-1+ or PD-1high (%) . | Prognostic effect . |
|---|---|---|---|---|---|
| HL | |||||
| 42 | cHL (189) | AF 1086 (R&D Systems, Wiesbaden-Nordenstadt) | 23 cells per mm2 PD-1+ infiltrating T cells | 52 | Increased tumor-infiltrating PD-1+ T cells correlated with poorer OS independently of stage of disease. However, in multivariable analysis for OS, PD-1+ cell count lost its significance as an independent prognostic factor. |
| 45 | cHL (122) | NAT (Abcam) | >15 cells per high-power field or >0.5% of all nucleated cells | ∼18 | PD-1 expression was associated with poor 5-year DSS in univariable analysis and poor OS in multivariable analysis. |
| FL/CLL | |||||
| 47 | FL (132) | NAT105 (Abcam) | Cutoffs for low and high proportion of PD-1+ cells in the diagnostic biopsies were ≤5% and >33%, respectively | ∼76 (PD-1+ cells >5%) and ∼25 (PD-1+ cells >33%) | Low proportion of PD-1+ cells in FL tissues was associated with poor OS and DLBCL transformation; high proportion of PD-1+ cells in FL tissues correlated with better OS and PFS. |
| 49 | FL (70) | (Spanish National Cancer Research Centre) | The good-outcome group had higher follicular PD-1+ cell densities than the poor-outcome group. | ||
| 51 | FL (91) | NAT (Abcam) | ≥35.6 cells per high-power field | 49 | Increased follicular PD-1+ cell density was an independent prognostic factor for poor OS. |
| 46 | FL (46); secondary DLBCL arising from FL (9); CLL (42) | Polyclonal AF1086 (R&D Systems) | 168 cells per mm2 or 2.8% of visible cells | 36 | Increased PD-1+ TILs were associated with favorable DSS in combined 55 cases of FL and secondary DLBCL arising from FL; the amount of PD-1+ TILs decreased from FL grade 1 to grade 3 and to FL with transformation to DLBCL; the amount of PD-1+ TILs was not prognostic in CLL. |
| 53 | CLL (71); FL (59) | Clone MIH4 (phycoerythrin); ab52597, NAT (Abcam) | CLL patients with poorer OS had increased PD-1 expression (IHC mean intensity) on T cells in CLL lymph node samples; FL patients with poorer OS had increased PD-1 expression (IHC mean intensity) on interfollicular T cells; transformation to DLBCL was associated with increased PD-1 expression (IHC mean intensity) compared with paired pretransformation FL samples. | ||
| 55 | FL treated with R-CHOP (82) | NAT, ab52587 (Abcam) | PD-1+ cells >14.4% of all nucleated cells | In >50% of male patients | High percentage of PD-1+ cells in FL biopsies was associated with poorer PFS in male patients (n = 43). |
| 50 | FL (58) | NAT (Abcam) | Diffuse staining pattern rather than the quantity of cells | 33 | The presence of PD-1+ cells in FL samples with a diffuse staining pattern (mostly not in the follicle) was associated with a shorter time to transformation and inferior OS. |
| 52 | FL (32) | ab52587 (Abcam) | >26% for CD4+ cells; >45% for CD8+ T cells | 50 | High PD-1+ percentage in interfollicular CD4+/CD8+ T cells with dim intensity significantly correlated with reduced OS; CD4+ T cells with bright intensity residing in the lymph node follicles were not associated with survival. |
| 54 | FL (92); transformed FL (52); nontransformed FL (40) | Polyclonal HPA035981 (Sigma Life Science) | Increased intrafollicular PD-1+ cell numbers in diagnostic biopsies were associated with transformation; the number of intrafollicular PD-1+ cells was significantly decreased upon transformation. | ||
| DLBCL | |||||
| 46 | DLBCL (138) | Polyclonal AF1086 (R&D Systems) | The amount of PD-1+ TILs was not associated with survival. | ||
| 56 | DLBCL (70) | Median of cell counts under high-power fields | 50 | High amounts of PD-1+ cells, FOXP3+ cells, and CD4+ T cells were all associated with improved clinical outcome. | |
| 57 | DLBCL (236) | Clone NAT105 (Abcam) | The median number of PD-1+ TILs | 50 | Unclear. |
| 64 | DLBCL (46) | (eBioscience) | 38.7 | High PD-1 levels (percentage expression) on T cells in the peripheral blood correlated with low effective rate of chemotherapy. | |
| 58 | DLBCL (126) | Clone MRQ-22 (Cell Marque) | >0 PD-1+ cells | 68.6 | Presence of tumor-infiltrating PD-1+ cells correlated with prolonged PFS (P = .005) and OS (P = .026). |
| 65 | DLBCL (60) | Clone MIH4 (phycoerythrin) | PD-1+ percentage in peripheral blood CD4+ T cells ≥30.25% | 16.7 | High PD-1+ percentage expression on CD4+ T cells in the peripheral blood correlated with poor EFS and OS. |
| 59 | DLBCL (76) | MRQ-22 (ZSGB-BIO) | Presence of PD-1+ cells | 39.5 | Presence of PD-1+ TILs in DLBCL tissues was associated with prolonged OS. |
| 63 | DLBCL (102) | (AbD Serotec) | PD-1+ cells accounting for 13.1% of all cells | 50 | High PD-1+ cell numbers were associated with poor survival. |
| Reference . | Lymphoma (No. of patients with follow-up) . | Antibody (manufacturer or source) . | PD-1+/high cutoff . | Prevalence of PD-1+ or PD-1high (%) . | Prognostic effect . |
|---|---|---|---|---|---|
| HL | |||||
| 42 | cHL (189) | AF 1086 (R&D Systems, Wiesbaden-Nordenstadt) | 23 cells per mm2 PD-1+ infiltrating T cells | 52 | Increased tumor-infiltrating PD-1+ T cells correlated with poorer OS independently of stage of disease. However, in multivariable analysis for OS, PD-1+ cell count lost its significance as an independent prognostic factor. |
| 45 | cHL (122) | NAT (Abcam) | >15 cells per high-power field or >0.5% of all nucleated cells | ∼18 | PD-1 expression was associated with poor 5-year DSS in univariable analysis and poor OS in multivariable analysis. |
| FL/CLL | |||||
| 47 | FL (132) | NAT105 (Abcam) | Cutoffs for low and high proportion of PD-1+ cells in the diagnostic biopsies were ≤5% and >33%, respectively | ∼76 (PD-1+ cells >5%) and ∼25 (PD-1+ cells >33%) | Low proportion of PD-1+ cells in FL tissues was associated with poor OS and DLBCL transformation; high proportion of PD-1+ cells in FL tissues correlated with better OS and PFS. |
| 49 | FL (70) | (Spanish National Cancer Research Centre) | The good-outcome group had higher follicular PD-1+ cell densities than the poor-outcome group. | ||
| 51 | FL (91) | NAT (Abcam) | ≥35.6 cells per high-power field | 49 | Increased follicular PD-1+ cell density was an independent prognostic factor for poor OS. |
| 46 | FL (46); secondary DLBCL arising from FL (9); CLL (42) | Polyclonal AF1086 (R&D Systems) | 168 cells per mm2 or 2.8% of visible cells | 36 | Increased PD-1+ TILs were associated with favorable DSS in combined 55 cases of FL and secondary DLBCL arising from FL; the amount of PD-1+ TILs decreased from FL grade 1 to grade 3 and to FL with transformation to DLBCL; the amount of PD-1+ TILs was not prognostic in CLL. |
| 53 | CLL (71); FL (59) | Clone MIH4 (phycoerythrin); ab52597, NAT (Abcam) | CLL patients with poorer OS had increased PD-1 expression (IHC mean intensity) on T cells in CLL lymph node samples; FL patients with poorer OS had increased PD-1 expression (IHC mean intensity) on interfollicular T cells; transformation to DLBCL was associated with increased PD-1 expression (IHC mean intensity) compared with paired pretransformation FL samples. | ||
| 55 | FL treated with R-CHOP (82) | NAT, ab52587 (Abcam) | PD-1+ cells >14.4% of all nucleated cells | In >50% of male patients | High percentage of PD-1+ cells in FL biopsies was associated with poorer PFS in male patients (n = 43). |
| 50 | FL (58) | NAT (Abcam) | Diffuse staining pattern rather than the quantity of cells | 33 | The presence of PD-1+ cells in FL samples with a diffuse staining pattern (mostly not in the follicle) was associated with a shorter time to transformation and inferior OS. |
| 52 | FL (32) | ab52587 (Abcam) | >26% for CD4+ cells; >45% for CD8+ T cells | 50 | High PD-1+ percentage in interfollicular CD4+/CD8+ T cells with dim intensity significantly correlated with reduced OS; CD4+ T cells with bright intensity residing in the lymph node follicles were not associated with survival. |
| 54 | FL (92); transformed FL (52); nontransformed FL (40) | Polyclonal HPA035981 (Sigma Life Science) | Increased intrafollicular PD-1+ cell numbers in diagnostic biopsies were associated with transformation; the number of intrafollicular PD-1+ cells was significantly decreased upon transformation. | ||
| DLBCL | |||||
| 46 | DLBCL (138) | Polyclonal AF1086 (R&D Systems) | The amount of PD-1+ TILs was not associated with survival. | ||
| 56 | DLBCL (70) | Median of cell counts under high-power fields | 50 | High amounts of PD-1+ cells, FOXP3+ cells, and CD4+ T cells were all associated with improved clinical outcome. | |
| 57 | DLBCL (236) | Clone NAT105 (Abcam) | The median number of PD-1+ TILs | 50 | Unclear. |
| 64 | DLBCL (46) | (eBioscience) | 38.7 | High PD-1 levels (percentage expression) on T cells in the peripheral blood correlated with low effective rate of chemotherapy. | |
| 58 | DLBCL (126) | Clone MRQ-22 (Cell Marque) | >0 PD-1+ cells | 68.6 | Presence of tumor-infiltrating PD-1+ cells correlated with prolonged PFS (P = .005) and OS (P = .026). |
| 65 | DLBCL (60) | Clone MIH4 (phycoerythrin) | PD-1+ percentage in peripheral blood CD4+ T cells ≥30.25% | 16.7 | High PD-1+ percentage expression on CD4+ T cells in the peripheral blood correlated with poor EFS and OS. |
| 59 | DLBCL (76) | MRQ-22 (ZSGB-BIO) | Presence of PD-1+ cells | 39.5 | Presence of PD-1+ TILs in DLBCL tissues was associated with prolonged OS. |
| 63 | DLBCL (102) | (AbD Serotec) | PD-1+ cells accounting for 13.1% of all cells | 50 | High PD-1+ cell numbers were associated with poor survival. |
Anti-PD-1 clone names were not available in references 49, 63, and 64.
DSS, disease-specific survival; EFS, event-free survival; IHC, immunohistochemistry; R-CHOP, rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone.