Table 5.
Lymphocyte Phenotyping.
| Assay | Study | Phase | Immunological Outcome | Immunological Correlation with Clinical Outcome |
|---|---|---|---|---|
| Complete Differential Blood Count | Bloch O, et al (2014) | II | 14/41 patients demonstrated absolute lymphocyte count (ALC) above lower limit of normal | ALC ≥ median demonstrated improved survival (p = 0.039); WBC count and absolute monocyte count did not predict survival |
| Ishikawa E, et al (2014) | I/IIa | 2/23 patients with CTCAE Grade 1 lymphopenia prior to vaccination, 7/23 with Grade 2 lymphopenia, 8/23 with Grade 3 lymphopenia; 6/23 with Grade 4 lymphopenia | Patients with Grade 3 lymphopenia exhibited superior OS compared to patients with Grade 0–2 and Grade 4 lymphopenia (p = 0.024) | |
| PBMC Flow Cytometry | Yamanaka R, et al (2003) | I/II | 0/5 patients with changes in CD3 or CD4; 4/5 patients with slight increases in CD8, CD 16, and CD 19; 5/5 patients with changes in CD56 (p < 0.05) | 4/5 patients with shift in CD56 had at least a minor response when evaluated by MRI |
| Ardon H, et al (2010) | Pilot | 6/7 patients demonstrated increased post-vaccination proportion of CD8+CD25+ T cells | No correlation between increased CD8+CD35+ T cells and clinical response | |
| Crane CA, et al (2013) | I | CD4 and CD8 frequencies stable pre/post vaccination; Expansion of CD3+CD4+CD8+ population in immune responders (11/12); Expansion of CD4+CD25+FoxP3+ Treg population in immune non-responder (1/12) | CD3+CD4+CD8+ population distinguished responders with increased OS; Expansion of CD4+CD25+FoxP3+ Treg cell population distinguished non-responder with decreased OS | |
| Kikuchi T, et al (2001) | I | No consistent post-vaccination shifts in CD3, CD4, CD8, and CD19; Slightly increased post-vaccination CD 16 and CD56 frequencies in 4/5 pts | 2 clinically minor responses observed – 2/2 exhibited increased CD16 and CD56 frequencies | |
| Jie X, et al (2012) | Prospective case-control | CD3+, CD3+CD4+, CD4+/CD8+, and NK cell populations increased in vaccine vs. control (p < 0.05) | OS increased for vaccine vs. control (p < 0.05); Time to recurrence prolonged for vaccine vs. control (p = 0.04) | |
| Olin MR, et al (2014) | Pilot | 3/9 patients exhibited significant decreases in lineageneg and monocytic MDSCs (p < 0.05); 6/9 patients demonstrated a significant increase in percentage of granulocytic MDSCs | Stable disease associated with decreased lineageneg and monocytic MDSCs vs. non-stable disease associated with increased proportion of granulocytic MDSCs; No difference in Tregs across stable and non-stable disease; Significant increase in CD8+ central memory T cells in stable disease population (p = 0.037) | |
| Prins RM, et al (2013) | I | Significantly increased NK cell proportion in GAA-DC trial (p < 0.0001) | Decreased Treg ratio (post/pre vaccination) associated with improved survival (p = 0.004); Decreased ratio of activated NK cell (post/pre vaccination) demonstrated a trend towards improved survival (p = 0.081) | |
| Fong B, et al (2012) | I | No significant pre/post vaccination shifts in CD4, CD8, NK T cells, NK cells, or Treg cell populations; No significant pre/post alteration in PD-1 on any lymphocyte subset | Decreased Treg ratio (post/pre vaccination) associated with improved survival (p=0.0228); Decreased CTLA4 expression by CD3+CD4+ T cells was associated with improved survival (p = 0.0191); Decreased CTLA4 expression by CD3+CD8+ T cells was associated with increased survival (p = 0.0460) | |
| Prins RM, et al (2011) | I | Vaccinated patients possessed increased CD3+CD4+FoxP3+ and CD3+CD4+CD25+FoxP3+ lymphocytes compared to healthy volunteers | No relevant changes in Treg populations that correlated with clinical outcome | |
| Ardon H, et al (2012) | I/II | Median pre-vaccine/post-vaccine ratios of lymphocyte populations: CD4 =1.01, CD8 = 1.08, NK = 0.89, Treg = 1.28 | No significant correlations between NK, Treg, CD4, or CD8 population shifts and PFS or OS; Cluster analysis of Treg and NK cell ratios produced several clusters with non-significant trends towards increased PFS | |
| Pellegata S, et al (2013) | Pilot | 6/14 patients exhibited increased post-vaccination NK cell frequency | Increased post/pre vaccination ratio of NK cells correlated with increased PFS (p = 0.004) and OS (p = 0.02) | |
| Kikuchi T, et al (2004) | Pilot | 7/7 patients demonstrated no significant changes in pre/post vaccination CD3, CD4, CD8, CD16, CD19, and CD56 surface phenotypes | - | |
| Phosphoflow | Everson RG, et al (2014) | I | 7/15 patients demonstrated pre/post vaccination pSTAT5 ratio > 1.065 in CTLs | Patients with increased pSTAT5 ratio demonstrated increased OS (p = 0.0015); Patients with survival > 2 years demonstrated increased pSTAT5 ratios (p = 0.015) and lower pSTATl ratios (p = 0.038) |