Table 1

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

Setting	Treatment	Indication	N	Sampling timepoints	Modality of CD8 assessment	Change in T-cell density	Reference
Neoadjuvant	1 cycle pembrolizumab	Melanoma	27	3 weeks	IHC	Increase in CD8 +T cells after therapy	39
Neoadjuvant	1 cycle ipilimumab +2 cycles nivolumab	Colon carcinoma	40	6 weeks	IHC	Higher baseline CD8 expression in dMMR tumors. Expansion of CD8 +T cells for both groups, although more pronounced in dMMR tumors	40
Neoadjuvant	2 cycles durvalumab +tremelimumab	Urothelial carcinoma	28	8–10 weeks	Cytometry by time-of-flight	Increase in ICOS +CD4+T cells in tumor lesion of responders (n=5), no change in non-responders. CD8 IHC not reported	41
Neoadjuvant	1 cycle pembrolizumab	HNSCC	36	13–22 days	RNA sequencing	No changes in CD8 +T cells	42
Neoadjuvant	4 cycles nivolumab or 3 cycles ipilimumab +nivolumab	Melanoma	23	Biopsy week 3–5 and resection after 8–9 weeks	IHC	Increase in CD8 +T cells in on-treatment biopsy for responders	43
Neoadjuvant	3 cycles MEDI6469 (OX40 agonist)	HNSCC	17	8–19 days	Multicolor flow cytometry and multiplex IHC	No change in IHC T cell densities	44
Neoadjuvant	1 cycle nivolumab or placebo	Glioblastoma	30	15 days	Multiplex immunofluorescence	No change in IHC T cell densities	45
Neoadjuvant	2 cycles durvalumab ±tremelimumab	HNSCC	28	Days 52–72	IHC	No difference in CD8 +T cells in patients with a major pathological response and non-responders	46
Neoadjuvant	3 cycles paclitaxel/carboplatin/nivolumab	Non-small cell lung cancer	46	Days 84–91	Multiplex immunofluorescence	Decrease in CD8 +T cell density after treatment	47
Neoadjuvant	2 cycles pembrolizumab +IFNα−2b	Melanoma	30	6 weeks	Fluorescence IHC	Expansion of CD8 +T cells and T_regs during treatment for the cohort as a whole	48
Serial biopsies	CTLA-4 blockade and/ or PD-1 blockade	Melanoma	53	Baseline, early on treatment (2–3 doses), and at progression	IHC	Increase in CD8 +T cells in responders	34
Serial biopsies	Pembrolizumab	Melanoma	46	Baseline 20–60 days 80–120 days 120 days	IHC	Increase in CD8 T cell density in responders. Stable CD8 numbers in non-responders	49
Serial biopsies	Pembrolizumab	Melanoma	53	Baseline and on-treatment (median 74 days)	cell single-cell flow cytometry analysis	Increase in T cell frequency. Increase in CD8 +effector memory T cells in responders	50
Serial biopsies	Anti-PD1 therapy (not specified)	Melanoma	13	Baseline and early on treatment (14 days)	Multiplex immunofluorescence	Expansion of CD8 +T cells	35
Serial biopsies	Pembrolizumab or nivolumab	Melanoma	23	Baseline and early on-treatment (<2 months)	IHC	Increase of CD68 +macrophages and CD8 +T cells in responders	51
Serial biopsies	Atezolizumab+bevacizumab	Renal cell cancer	10	Baseline, 15–18 days after bevacizumab and 4–6 weeks after start atezolizumab/ bevacizumab.	IHC	No increase in CD8 after atezolizumab/bevacizumab treatment	52
Serial biopsies	Nivolumab with or without ipilimumab	Melanoma	101	Baseline and week 2 or 4 on treatment	RNA sequencing	Increase in CD8 +T cells in responders	53

dMMR, deficient mismatch repair; HNSCC, head and neck squamous cell carcinoma; ICOS, inducible T cell co-stimulator; IFN, interferon; IHC, immunohistochemistry; T_regs, regulatory T cells.