Microwave ablation combined with anti-PD-1/CTLA-4 therapy induces an antitumor immune response to renal cell carcinoma in a murine model

Figures & data

Figure 1. Experimental design and schedule. (a) the assessment of tumor growth at each time point. (b) the arrangement of the rechallenge test. MWA: microwave ablation.

Figure 2. MWA+ICI combination treatment obviously suppresses tumor growth rate. (a) the volume of untreated tumors within 21 days. (b) Specific growth rate (SGRs) of tumors in control, MWA, ICI, and MWA+ICI groups. *P<.05, **P<.01. MWA: microwave ablation; ICI: immune checkpoint inhibitor; SGR: specific growth rate.

Table 1. Growth of untreated tumors.

Treatment	Mean tumor volume (cm^3)				Mean tumor volume upon rechallenge (cm^3)
	Day 0	Day 7	Day 14	Day 21	Day 14	Day 21
Control	0.143±0.042 (n=6)	0.898±0.224 (n=6)	2.202±0.666 (n=6)	5.510±1.311 (n=5)	0.127±0.024 (n=6)	0.953±0.271 (n=6)
MWA	0.133±0.064 (n=6)	0.914±0.294 (n=6)	1.721±0.838 (n=5)	3.390±1.433 (n=5)	0.149±0.057 (n=6)	0.802±0.317 (n=6)
ICI	0.128±0.043 (n=6)	0.335±0.114 (n=6)	1.800±0.527 (n=6)	2.909±0.596 (n=6)	0.162±0.027 (n=6)	0.383±0.079 (n=6)
MWA+ICI	0.151±0.096 (n=6)	0.243±0.091 (n=6)	1.490±0.445 (n=6)	2.331±0.425 (n=6)	0.131±0.050 (n=6)	0.334±0.047 (n=6)

MWA, microwave ablation; ICI, immune checkpoint inhibitor.

Figure 3. MWA+ICI combination treatment increases CD8+T-cell percentage and decreases Treg cell population. (a) CD8+T-cell percentage in control, MWA, ICI, and MWA+ICI groups. (b) Treg population by group. (c) MDSC population by group. (d) CD8+T/Treg ratio by group. (e) IFN-γ levels by group. *P<.05, **P<.01, ***P<.001, ****P<.0001.

Figure 4. Detection of CTLA4, PD-L1 and PD-1 expression levels in distant tumors. (a) Mean density of CTLA4 expression in tumor tissues of control, MWA, ICI, and MWA+ICI groups. (b) Mean density of PD-L1 expression by group. (c) Mean density of PD-1 expression by group. *P<.05, **P<.01. MWA: microwave ablation; ICI: immune checkpoint inhibitor.

Figure 5. Upon rechallenge test, MWA+ICI combination treatment boosts tumor rejection. (a) Volumes of distant tumors in control, MWA, ICI, and MWA+ICI groups. (b) SGRs by group. (c) CD8+T-cell percentage by group. (d) Treg cell population by group. (e) MDSC population by group. (f) CD8+T/Treg ratio by group. (g) IFN-γ levels by group. *P<.05, **P<.01, ***P<.001, ****P<.0001.

Figure 6. Immunodeficient mice exhibits no tumor rejection after the combination therapy. (a) Volumes of tumors in Rag1^−/− mice of control, MWA, ICI, and MWA+ICI groups at the time point of day 0, day 7, day 14, and day 21. (b) SGRs of tumors in Rag1^−/− mice from above four groups. (c) CD8+T-cell percentage by group. (d) Treg cell population by group. (e) MDSC population by group. (f) CD8+T/Treg ratio by group. (g) IFN-γ levels by group.