Thermal Ablative Therapies and Immune Checkpoint Modulation: Can Locoregional Approaches Effect a Systemic Response?

Table 1

Selected publications surveying the clinical and preclinical evidence for immunomodulatory effects of RFA and cryoablation.

Modality	Cell type	Immune component	Species	Ref.
RFA
Potential tumor suppression
	VX2	tumor-specific T-cells; T-cell infiltration	Rabbit	[44]
	HCC	DC activation; serum TNF-, IL-1	Human	[31]
	HCC	Tumor-specific CD4+ and CD8+ response	Human	[90]
	HCC	HSP70 in tumor cell surface and cytoplasm	Human	[91]
	Primary and metastatic liver, kidney, and lung cancer	HSP70	Human	[41]
	Primary and metastatic liver tumors	memory T-cell trafficking, T-cell proliferation in metastatic cancer patients	Human	[92]
	HCC	tumor-specific CD8+, correlating with progression-free survival after ablation	Human	[43]
	Primary and metastatic lung tumors	; serum IL-8, IL-10, C3, C4, and CRP	Human	[32]
	Colon and kidney tumors and melanoma	antigen-specific antibodies, CD4+ and CD8+ T-cells	Human	[46]
	HCC	NK cell stimulation	Human	[93]
	Primary and metastatic colon, liver, kidney, and lung tumors, melanoma, and sarcoma	serum IL-6, IL-10; serum TNF-, IL-1, and IL-2	Human	[33]
	Melanoma	Reduced tumor recurrence when combined with DC tumoral vaccine	Mouse	[86]
	Melanoma	DC activation; immunization against rechallenge with anti-CTLA-4 therapy	Mouse	[9, 94]
	Urothelial cancer	Tumor-specific T-cell activation, immunization against rechallenge	Mouse	[37]
	Hepatocytes	IL-6	Rat	[34]
	Hepatocytes	apoptosis, HSP70 in transition zone	Pig	[95]
Potential tumor stimulation
	Hepatocytes	intracellular HSP70 expression in tumor cells near blood vessels	Rat	[96]
	Hepatocytes (MDR2 knockout)	tumor development, survival; effect diminished with c-Met inhibitor	Mouse	[3]
	Hepatocytes	breast cancer xenograft growth; effect diminished with c-Met/VEGF inhibitors	Rat	[47]
	Colorectal	hypoxia, HIF-1, and HIF-2 in transition zone leading to tumor growth	Mouse/rat	[49]
	HCC	HIF-1, VEGF, and angiogenesis	Mouse	[51]
	Hepatocytes	breast cancer xenograft growth; effect diminished with anti-IL-6 siRNA	Mouse/rat	[54]
Cryoablation
Potential tumor suppression
	Prostate	Remission of metastases following prostate cryoablation	Human	[55, 58]
	Sarcoma	Regression of remote tumor; immunization against rechallenge	Rat	[57]
	Breast	Tumor-specific T-cell response; immunization against rechallenge	Mouse	[61]
	Melanoma	Combination with TLR9 stimulation reduces local and remote tumors	Mouse	[83]
	Melanoma	DC activation; immunization against rechallenge with anti-CTLA-4 therapy	Mouse	[9]
	HCC	IL-6, CRP, and IL-10; TNF- and Th1/Th2 associated with remote tumor regression	Human	[97]
	Prostate	TNF-, IFN-, and Th1/Th2; tumor-specific T-cell response	Human	[98]
	Lung metastases	Combination with GM-CSF caused tumor-specific T-cell response and anti-tumor antibodies	Human	[88]
	Lung tumor, melanoma	Combination with DC therapy tumor-specific CD8+ T-cell response, survival	Mouse	[82]
	Colon	DC + Bacillus Calmette-Guérin cell wall skeleton caused tumor-specific CD8+ T-cell response and local and remote tumor regression	Mouse	[99]
Potential tumor suppression
	Fibrosarcoma	mortality from metastases compared to surgical excision; excision of cryoablated tumor reduced rate of metastasis	Rat	[64]
	Fibrosarcoma	growth of pulmonary metastases after cryoablation of flank tumor	Rat	[65]
	Breast	Low freeze rate can , remote metastases, and survival	Mouse	[68]