More Than Just Tumor Destruction: Immunomodulation by Thermal Ablation of Cancer

Table 1

Thermal ablative methods in clinical use for the treatment of cancer and described effects on the immune system.

			Immune Modulation
Treatment	Indication	Characteristics/principle	Component	Effect	Ref.	Species
Radiofrequency	Clinical indication: primary and	Mechanism: application of	Cytokines	+	[51–54]	Human
(RF) ablation	secondary malignancies in liver,	alternating RF current through tip	Danger	+	[55–61]	Animal
	kidney, lung, and bone	applicator placed around and in	signals	+	[62, 63]	Human
	[2, 8, 17, 49]	tumor tissue resulting in heat and	Granulocytes	+	[64, 65]	Animal
		coagulative necrosis			[54, 66]	Human
	Experimental application: tumors		NK cells	+	[61]	Animal
	of the breast [50]	Approach: percutaneous, open,		+	[67]	Human
		and intraoperative	Monocytes/	+	[66]	Animal
			Macrophages
		Image guidance: US, CT, and MRI	DC	+	[68, 69]	Animal
					[51]	Human
			T cells*	+	[49, 57, 65, 68–74]	Animal
				+	[70, 75–78]	Human
			Treg	−	[54]	Human
			B cells	+	[75]	Human
			Antibodies*	+	[78]	Human
Cryoablation	Clinical indication: primary and	Mechanism: application of cold	Cytokines	+	[39, 83]	Animal
	secondary malignancies in liver,	through gaseous evaporation at		+	[36, 84, 85]	Human
	kidney, and prostate, as well as	the tip of a cryoprobe. Repetitive	Danger	?
	dermatologic and ophthalmologic	freezing and thawing cycles lead to	signals
	tumors [4, 33, 79, 80].	direct cellular damage through ice	Granulocytes	+	[86]	Animal
	Experimental Application: tumors	crystals, vascular and endothelial	NK cells	+	[83]	Animal
	of the breast [81].	injury, and eventually thrombosis		+	[87]	Human
		and ischemia [79, 82] resulting in	Monocytes/	+	[86, 88]	Animal
		coagulative necrosis and apoptosis	Macrophages
		at the ablation margin	DC	+	[69]	Animal
		Approach: percutaneous, open,	T cells	+	[38, 69, 79, 83, 89–98]	Animal
		intraoperative		+	[85, 87, 99–102]	Human
			Treg	+	[103, 104]	Animal
				−	[105]	Human
		Image guidance: US, CT, and MRI	B cells	+	[91]	Animal
			Antibodies*	+	[86, 106–113]	Animal
				+	[41, 87, 114–116]	Human
Microwave	Clinical indication: mainly used for	Mechanism: application of	Cytokines	?	[117]	Animal
ablation therapy	treatment of HCC, but also other	microwaves through tip applicator	Danger	+
(MWA)	primary and	leading to coagulative necrosis	signals
	secondary	[21]	Granulocytes	?
	malignancies of the liver [21, 22]		NK cells	+	[118]	Animal
		Approach: percutaneous, open,		+	[119]	Human
		and intraoperative	Monocytes/	+	[119]	Human
			Macrophages
			DC	?
		Image guidance: US, CT, and MRI	T cells	+	[118]	Animal
				+	[22, 119, 120]	Human
			Treg	?
			B cells	+	[22]	Human
			Antibodies	?
High-intensity	Experimental application: primary	Mechanism: application of focused	Cytokines	?
focused	and secondary malignancies in	ultrasound beams of	Danger	+	[122]	Human
Ultrasound	breast, liver, pancreas, kidney,	high-intensity resulting in	signals
(HIFU)	bone, prostate, and	coagulative necrosis	Granulocytes	?
	soft-tissue-tumors [121]		NK cells	+	[123]	Human
			Monocytes/	?
		Approach: noninvasive	Macrophages
			DC	?
		Image guidance: noninvasive	T cells	+	[121, 124]	Animal
		real-time US		+	[27, 125, 126]	Human
			Treg	?
			B cells	+	[27]	Human
			Antibodies	?
Laser induced	Clinical indication: broadly applied	Mechanism: placement of multiple	Cytokines	+	[130]	Human
thermotherapy	for photocoagulation in retinal	simultaneous fired laser fibers into	Danger signals	+	[131]	Animal
(LITT)	disease [127], primary, and	a tumor resulting in coagulative necrosis [129]	Granulocytes
	secondary malignancies of the		NK cells	?
	liver [128]
	Experimental application: primary	Approach: percutaneous	Monocytes/	?
	and secondary malignancies of the		Macrophages
	breast, brain, bone, and prostate		DC	?
	[129]	Image guidance: MRI, CT, and US	T cells	+	[128, 132]	Animal
			Treg	?
			B cells	?
			Antibodies	?

Asterisks indicate allocation of T-cell or antibody responses to defined antigens.
Ref., reference number.