Immune-cell infiltration in high-grade soft tissue sarcomas; prognostic implications of tumor-associated macrophages and B-cells

Figures & data

Table 1. Clinical and prognostic factors in relation to histotype.

Characteristics	Total cohort N = 134 (%)	LMS (n = 65)	LPS (n = 47)	SS (n = 22)	p-value
Age at diagnosis
Median (range)	63 (23–94)	74 (29–94)	60 (23–86)	36.5 (24–72)	<0.001
Gender
Female	73 (54)	37 (57)	26 (55)	10 (54)	0.64
Male	61 (46)	28 (43)	21 (45)	12 (56)
Tumor size (cm)
<8	62 (46)	37 (57)	10 (21)	15 (68)	<0.001
> =8	72 (54)	28 (43)	37 (79)	7 (32)
Grade
low (I + II)	18 (14)	0	18 (40)	0	<0.001
high (III + IV)	113 (86)	65 (100)	27 (60)	21 (100)
unknown	3	0	2	1
Tumor depth
Superficial	34 (26)	23 (36)	9 (20)	2 (9)	0.023
Deep	98 (74)	41 (64)	37 (80)	20 (91)
unknown	2	1	1	0
Vascular Invasion
present	29 (23)	17 (27)	6 (14)	6 (29)	0.21
absent	99 (77)	46 (73)	38 (86)	15 (71)
unknown	6	2	3	1
Tumor Necrosis
present	71 (54)	20 (31)	17 (37)	9 (41)	0.002
absent	61 (46)	45 (69)	29 (63)	12 (55)
unknown	2	0	1	1
Growth Pattern
pushing	15 (22)	2 (6)	11 (52)	2 (18)	<0.001
infiltrating	53 (78)	34 (94)	10 (48)	9 (82)
unknown	66	29	26	10
Local recurrence
No	112 (84)	53 (82)	42 (89)	17 (77)	0.37
Yes	22 (16)	12 (18)	5 (11)	5 (16)
Distant metastasis
No	79 (59)	31 (48)	36 (77)	12 (55)	0.008
Yes	55 (41)	34 (52)	11 (23)	10 (46)
Postoperative radiotherapy
No	80 (60)	33 (51)	33 (70)	14 (64)	0.11
Yes	54 (40)	32 (49)	14 (30)	8 (36)
Adjuvant chemotherapy
No	122 (91)	60 (92)	45 (96)	17 (77)	0.038
Yes	12 (9)	5 (8)	2 (4)	5 (23)
Follow-up time (months)
median (range)	78 (2–300)	42 (2–244)	107 (6–290)	100 (18–300)
Follow-up status
alive	40 (30)	10 (15)	20 (43)	10 (45)	0.0020
dead	94 (70)	55 (85)	27 (57)	12 (55)

Figure 1. Representative microscope (x20) photographs of immunohistochemical immune cell markers (CD8, cytotoxic T-cells; CD3, peripheral T-cells; CD20, precursor and mature B-cells; FOXP3, regulatory T-cells; CD163, macrophage lineage) high expression in leiomyosarcomas (LMS).

Table 2. Spearman’s correlation between immune cell markers.

Table 3. Correlation between immune cell markers and known prognostic factors.

Immune marker		Size (>8cm) OR (95% CI) p-value	Necrosis OR (95% CI) p-value	Vascular invasion OR (95% CI) p-value	Grade OR (95% CI) p-value
CD163	Low	1.00	1.00	1.00	1.00
	High	1.07 (0.53–2.14) p = 0.85	3.22 (1.55–6.65) p = 0.002	2.31 (0.97–5.53) p = 0.059	2.96 (0.99–8.86) p = 0.053
CD20	Low	1.00	1.00	1.00	1.00
	High	1.26 (0.58–2.74) p = 0.55	0.92 (0.43–1.99) p = 0.84	0.52 (0.18–1.50) p = 0.22	0.70 (0.24–2.03) p = 0.51
CD3	Low	1.00	1.00	1.00	1.00
	High	0.42 (0.21–0.85) p = 0.016	1.76 (0.88–3.53) p = 0.11	0.86 (0.38–1.99) p = 0.73	2.79 (0.93–8.36) p = 0.066
CD8	Low	1.00	1.00	1.00	1.00
	High	0.48 (0.24–0.97) p = 0.041	2.06 (1.01–4.19) p = 0.047	1.02 (0.44–2.37) p = 0.96	4.33(1.19–15.81) p = 0.026
FOXP3	Low	1.00	1.00	1.00	*
	High	0.46 (0.19–1.12) p = 0.089	1.61 (0.65–3.98) p = 0.3	0.72 (0.22–2.34) p = 0.59	*

^a Not applicable. All events in same group.

Table 4. Metastasis-free and Overall Survival. Univariable and multivariable analyses.

Metastasis-Free Survival
	Whole Cohort (n = 113)	LMS (n = 65)	LPS (n = 26)	SS (n = 21)
Univariable Cox regression
Size >8cm	HR 3.59 p < 0.001 CI (1.99–6.48)	HR 4.19 p < 0.001 CI ( 2.06–8.51)	^*	HR 6.09 p = 0.012 CI (1.50–24.79)
Necrosis	HR 3.18 p < 0.001 CI (1.69–5.98)	HR 1.84 p = 0.12 CI ( 0.86–3.97)	HR 14.11 p = 0.012 CI (1.77–112.87)	HR 3.66 p = 0.069 CI (0.90-14.79)
Vascular Invasion	HR 2.49 p = 0.002 CI (1.41–4.40)	HR 2.30 p = 0.023 CI (1.12–4.72)	HR 3.29 p = 0.078 CI (0.88–12.32)	HR 2.46 p = 0.18 CI (0.65–9.23)
CD163	HR 1.81 p = 0.040 CI (1.03–3.19)	HR 1.44 p = 0.35 CI ( 0.67–3.10)	HR 3.93 p = 0.084 CI ( 0.83–18.62)	HR 0.94 p = 0.95 CI ( 0.12–7.54)
CD20	HR 0.78 p = 0.44 CI (0.42–1.46)	HR 0.71 p = 0.38 CI ( 0.33–1.52)	HR 0.78 p = 0.71 CI (0.20–3.01)	HR 0.61 p = 0.64 CI (0.076–4.88)
Multivariable Cox regression
CD163	HR 1.27 p = 0.44 CI (0.69–2.31)	HR 1.38 p = 0.45 CI (0.60–3.15)	HR 0.90 p = 0.91 CI (0.15–5.55)	HR 0.43 p = 0.48 CI (0.042– 4.41)
CD20	HR 0.56 p = 0.093 CI (0.28–1.10)	HR 0.36 p = 0.023 CI (0.15–0.87)	HR 0.53 p = 0.44 CI (0.11–2.68)	*
Overall Survival
	Whole cohort (n = 112)	LMS (n = 65)	LPS (n = 26)	SS (n = 22)
Univariable Cox regression
Size >8cm	HR 2.31 p = 0.001 CI (1.41–3.77)	HR 2.65 p = 0.001 CI ( 1.46–4.80)	HR 2.13 p = 0.32 CI (0.47–9.57)	HR 4.76 p = 0.029 CI (1.17–19.38)
Necrosis	HR 3.21 p < 0.001 CI (1.85–5.58)	HR 2.17 p = 0.027 CI ( 1.09–4.30)	HR 6.29 p = 0.005 CI (1.72–22.91)	HR 3.04 p = 0.12 CI (0.76–12.20)
Vascular Invasion	HR 1.97 p = 0.010 CI (1.18–3.28)	HR 1.76 p = 0.082 CI ( 0.93–3.35)	HR 3.22 p = 0.050 CI (1.00–10.38)	HR 1.85 p = 0.36 CI (0.50–6.91)
CD163	HR 1.59 p = 0.066 CI ( 0.97–2.59)	HR 1.06 p = 0.86 CI (0.56–2.01)	HR 2.98 p = 0.072 CI (0.91–9.81)	*
CD20	HR 0.54 p = 0.043 CI (0.29–0.98)	HR 0.44 p = 0.027 CI ( 0.21–0.91)	HR 0.71 p = 0.56 CI (0.22–2.25)	*
Multivariable Cox regression
CD163	HR 1.20 p = 0.49 CI (0.72–2.01)	HR 1.01 p = 0.97 CI (0.51–1.99)	HR 1.60 p = 0.50 CI (0.40–6.36)	*
CD20	HR 0.35 p = 0.003 CI (0.18–0.71)	HR 0.26 p = 0.002 (0.11–0.60)	HR 0.30 p = 0.51 CI (0.06–1.54)	*

* Not applicable. All events in same group.

Data availability statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.