Tumour-associated macrophages are related to progression in patients with metastatic melanoma following interleukin-2 based immunotherapy

Figures & data

Table I.  Patient characteristics.

Variable	n	%
Number of patients	27	100%
Median age, range	49 years	(31–65)
Sex
Female	11	41%
Male	16	59%
Performance status
0–1	22	81%
2	5	19%
Site of metastases
Skin/subcutaneous	24	89%
Lymph nodes	15	56%
Lung	13	48%
Liver	4	15%
Other sites	8	30%
No. of metastatic sites
1	6	22%
2	9	33%
3	9	33%
≥ 4	3	12%

Table II.  Leukocyte subpopulations in blood in relation to overall response.

	Responders (n1=9)		Non-responders (n2=14)
	Cell counts 10^9/L		Cell counts 10^9/L		Mann Whitney U
Leukocyte subsets	Median	Range	Median	Range	p	Probability*
CD4 (helper T cells)	0.40	0.12–0.63	0.56	0.27–1.51	0.06	73%
CD8 (cytotoxic T cells)	0.41	0.27–1.11	0.48	0.26–0.76	0.73	58%
CD56 (NK cells)	0.29	0.16–0.56	0.32	0.15–0.55	0.61	60%
Monocytes	0.44	0.30–2.48	0.63	0.36–1.47	0.10	64%

Responders (PR + CR). Non-responders (SD + PD). *The probability is calculated as U/(n₁*n₂) and is an estimate of the probability that a random count from group 1 (responders) is less than a random count from group 2 (non-responder) (50% means no difference).

Figure 1.  Immunohistochemical staining of CD64 + tumor-associated macrophages in a non-responding patient. Tumor-associated macrophages (black arrow) and tumor cells (white arrow).

Table III.  Leukocyte subpopulations in tumour biopsies in relation to overall response.

	Responders (n1=9)		Non-responders (n2=18)
	Cell counts/mm^3		Cell counts/mm^3		Mann Whitney U
Leukocyte subsets	Median	Range	Median	Range	p	Probability*
CD4 (helper T cells)	6207	830–14267	3776	485–17688	0.87	53%
CD8 (cytotoxic T cells)	3032	575–13004	4315	116–29623	0.40	56%
CD57 (NK cells)	923	125–2746	1281	107–5217	0.23	65%
CD64 (macrophages)	2847	843–8868	6612	3122–19043	0.007	84%

Responders (PR + CR). Non-responders (SD + PD). *The probability is calculated as U/(n₁*n₂) and is an estimate of the probability that a random count from group 1 (responders) is less than a random count from group 2 (non-responder) (50% means no difference).

Table IV.  Univariate and multivariate analyses of potential prognostic factors for overall survival.

	Univariate analysis			Multivariate analysis^§
Variables	HR	95% CI	p-value	HR	95% CI	p-value
Treatment 1 vs treatment 2	1.3	0.6–2.7	0.58
Performance status: 0–1 vs. 2	3.2	1.1–9.2	0.04	3.9	1.3–11.9	0.02
Number of sites: 1–2 vs. ≥3	4.6	1.4–10.2	0.002	4.3	1.6–11.6	0.004
LDH: Normal vs. elevated	2.5	1.1–5.7	0.04	1.8	0.7–4.3	0.19
CD4+ (blood)	1.4	0.6–3.3	0.47
CD8+ (blood)	1.0	0.4–2.3	0.99
CD56+ (blood)	1.1	0.5–2.6	0.83
Monocytes (blood)	1.6	0.7–3.6	0.21
CD4+ (biopsy)	0.9	0.4–2.0	0.80
CD8+ (biopsy)	1.3	0.6–2.9	0.57
CD57+ (biopsy)	1.9	0.8–4.4	0.15
CD64+ (biopsy)	0.7	0.3–1.6	0.37

95% CI, 95% confidence intervals; LDH, lactate dehydrogenase; Treatment 1, Cisplatinum, interleukin-2 and interferon; Treatment 2, Interleukin-2, interferon±histamine. ^§ n = 25 patients, 25 deaths.