Table 1

Overview of studies evaluating changes in T-cell infiltration following immune checkpoint inhibitor therapy

SettingTreatmentIndicationNSampling timepointsModality of CD8 assessmentChange in T-cell densityReference
Neoadjuvant1 cycle pembrolizumabMelanoma273 weeksIHCIncrease in CD8 +T cells after therapy39
Neoadjuvant1 cycle ipilimumab +2 cycles nivolumabColon carcinoma406 weeksIHCHigher baseline CD8 expression in dMMR tumors. Expansion of CD8 +T cells for both groups, although more pronounced in dMMR tumors40
Neoadjuvant2 cycles durvalumab +tremelimumabUrothelial carcinoma288–10 weeksCytometry by time-of-flightIncrease in ICOS +CD4+T cells in tumor lesion of responders (n=5), no change in non-responders. CD8 IHC not reported41
Neoadjuvant1 cycle pembrolizumabHNSCC3613–22 daysRNA sequencingNo changes in CD8 +T cells42
Neoadjuvant4 cycles nivolumab or 3 cycles ipilimumab +nivolumabMelanoma23Biopsy week 3–5 and resection after 8–9 weeksIHCIncrease in CD8 +T cells in on-treatment biopsy for responders43
Neoadjuvant3 cycles MEDI6469
(OX40 agonist)
HNSCC178–19 daysMulticolor flow cytometry and multiplex IHCNo change in IHC T cell densities44
Neoadjuvant1 cycle nivolumab or placeboGlioblastoma3015 daysMultiplex immunofluorescenceNo change in IHC T cell densities45
Neoadjuvant2 cycles durvalumab ±tremelimumabHNSCC28Days 52–72IHCNo difference in CD8 +T cells in patients with a major pathological response and non-responders46
Neoadjuvant3 cycles paclitaxel/carboplatin/nivolumabNon-small cell lung cancer46Days 84–91Multiplex immunofluorescenceDecrease in CD8 +T cell density after treatment47
Neoadjuvant2 cycles pembrolizumab +IFNα−2bMelanoma306 weeksFluorescence IHCExpansion of CD8 +T cells and Tregs during treatment for the cohort as a whole48
Serial biopsiesCTLA-4 blockade and/ or PD-1 blockadeMelanoma53Baseline, early on treatment (2–3 doses), and at progressionIHCIncrease in CD8 +T cells in responders34
Serial biopsiesPembrolizumabMelanoma46
  • Baseline

  • 20–60 days

  • 80–120 days

  • 120 days

IHCIncrease in CD8 T cell density in responders. Stable CD8 numbers in non-responders49
Serial biopsiesPembrolizumabMelanoma53Baseline and on-treatment (median 74 days)cell single-cell flow cytometry analysisIncrease in T cell frequency. Increase in CD8 +effector memory T cells in responders50
Serial biopsiesAnti-PD1 therapy (not specified)Melanoma13Baseline and early on treatment (14 days)Multiplex immunofluorescenceExpansion of CD8 +T cells35
Serial biopsiesPembrolizumab or nivolumabMelanoma23Baseline and early on-treatment (<2 months)IHCIncrease of CD68 +macrophages and CD8 +T cells in responders51
Serial biopsiesAtezolizumab+bevacizumabRenal cell cancer10Baseline, 15–18 days after bevacizumab and 4–6 weeks after start atezolizumab/ bevacizumab.IHCNo increase in CD8 after atezolizumab/bevacizumab treatment52
Serial biopsiesNivolumab with or without ipilimumabMelanoma101Baseline and week 2 or 4 on treatmentRNA sequencingIncrease in CD8 +T cells in responders53
  • dMMR, deficient mismatch repair; HNSCC, head and neck squamous cell carcinoma; ICOS, inducible T cell co-stimulator; IFN, interferon; IHC, immunohistochemistry; Tregs, regulatory T cells.