Table 1.
Four classes of the laser adjuvant.
| Class | Laser type | Wavelength | Pathway Activated | Immune responses stimulated | Tested in | References |
|---|---|---|---|---|---|---|
| Ultra-short pulsed laser (UPL) | Copper vapor | 511/578 nm | Extracellular release of HSP70 to enhance Langerhans cell activation and antigen presentation | Ab against influenza and hepatitis B Augment cancer vaccines |
Mice, humans | (21–23) |
| Q switched Nd:YAG | 532 nm | Migration and activation of APCs in the skin | Ab against influenza Ab and T cell responses against OVA |
Mice | (24) | |
| Potassium titanyl phosphate (KTP) | 532 nm | n.d. | Ab and T cell responses against OVA upon intramuscular injection | Mice | (24) | |
| Q switched Nd:YAG | 532 nm | Disarray of the extracellular matrix in the dermis facilitates migration of DCs | Cytotoxic T cell response against solid tumor | Mice | (84) | |
| Q switched Nd:YAG | 532 nm | n.d. | Ab against nicotine | Mice | (25) | |
| Q switched Nd:YVO4 | 532 or 1064 nm | A selective upregulation of chemokines and cytokines in the skin leading to APCs activation and migration | Ab against influenza and OVA | Mice | (26) | |
| Q switched Nd:YAG (532) Pulsed dye laser (595) |
532 and 595 nm | Increase in vascular permeability increases translocation of sporozoite to liver | Sporozoite-specific antibody and CD8+ T cell responses | Mice | (27) | |
| Non-pulsed laser (NPL) | Semiconductor laser | 980 nm | Photothermal effect induced cancer cell death and subsequent DC and CTL activation and recruitment in tumor microenvironment | CTL response against pancreatic cancer and melanoma | Mice | (32) |
| n.d. | 808 nm | Laser along with imiquimod induced intracellular expression of DAMPs | Suppression of tumor growth of skin SCC | Mice and Humans | (35) | |
| Diode laser | 805 nm | n.d. | Synergistic effects between laser immunotherapy and immune checkpoint inhibitor on tumor growth of melanoma | Humans | (36) | |
| Diode laser | 808 nm | Laser along with imiquimod treatment induced lymphocyte infiltration into warts | Suppression of tumor growth of refractory warts | Humans | (37) | |
| Diode laser | 980 nm | Photothermal effect induced cancer cell death and subsequent DC and CTL activation and recruitment in tumor microenvironment | Induction of tumor-specific CTLs in breast cancer model |
Mice | (34) | |
| n.d. | 808 nm | Photothermal effect induced thermal lysis of the tumor cell membrane and release of tumor-specific antigens | Maturation of DCs and induction of tumor infiltration of CTLs in breast cancer model | Mice | (38) | |
| CW Nd:YVO4 | 1064 nm | Photochemical reaction in skin tissue leading to immunostimulatory microenvironment for APCs via expression of a selective chemokines | Ab and T cell responses against influenza and OVA | Mice, human (no immunogenicity study) | (26) | |
| GaAs (1061) InP (1258, 1301), CW Nd:YVO4 (1064) |
1061, 1258, 1301 nm | n.d. | Ab response against influenza | Mice | (41) | |
| CW Nd:YVO4 | 1064 nm | Selective activation of Lang+ and Lang-CD11b- skin DCs and recruitment of Ly6C+ monocytes | Ab response against influenza | Mice | (42) | |
| CW Nd:YVO4 | 1064 nm | Photochemical reaction in mast cells and keratinocytes leading to ROS generation and chemokine/cytokine expression and immunostimulatory microenvironment for skin DCs | Ab response against influenza | Mice | (43) | |
| Custom diode laser | 1064 nm | n.d. | Induction of migration response of skin DCs | Human (no immunogenicity study) | (47) | |
| Non-ablative fractional laser (NAFL) | Fractional ER:Glass (PaloVia laser, mice; Fraxel SR-1500, pigs) | 1410 nm (mice) 1540 nm (pigs) |
Sterile inflammation caused by an array of MTZs in skin recruits pDCs | Ab and T cell responses against influenza with imiquimod | Mice, pigs | (49) |
| Fractional ER:Glass (PaloVia laser, mice; Fraxel SR-1500, pigs) | 1410 nm (mice) 1540 nm (pigs) |
Activation of dsDNA sensing pathway and subsequent interferon upregulation by MTZs in skin facilitates migration of DCs | Ab and T cell responses against influenza using microneedles | Mice, pigs | (51) | |
| Fractional ER:Glass (PaloVia laser) | 1410 nm | Adjuvant effect of micro-injury in skin | Ab against OVA using hyaluronan nanocarriers | Mice, pigs (no immunogenicity study) | (53) | |
| Fractional ER:Glass (PaloVia laser) | 1410 nm | Direct activation of skin-resident DCs | TEM and TRM CD8+ T cell responses against herpes virus with imiquimod | Mice | (52) | |
| Fractional ER:Glass (PaloVia laser) | 1410 nm | ATRA stimulated upregulation of cytosolic nucleic acid sensors and their downstream factors and enhanced type I interferon expression with NAFL | Ab against influenza with ATRA | Mice | (54) | |
| Ablative fractional laser (AFL) | Fractional CO2 (UltraPulse device) | 10600 nm | Efficient delivery of vaccine to skin DCs | Ab against OVA | Mice | (61) |
| Fractional CO2 (UltraPulse device) | 10600 nm | Efficient delivery of vaccine to skin DCs | Ab against OVA and T cell responses against OVA-expressing vaccinia virus | Mice, pigs (no immunogenicity study), humans (no immunogenicity study) | (65) | |
| Fractional ER:YAG (P.L.E.A.S.E. device) | 2940 nm | The mild inflammatory milieu created in the dermis activates skin-resident DCs and induces infiltration of APCs | T cell response against melanoma using a vaccibody targeting XCR1+ DCs | Mice | (66) | |
| Fractional ER:YAG (P.L.E.A.S.E. device) | 2940 nm | The limited inflammatory response activates Langerhans cells and facilitates DC migration | Ab response to OVA and recombinant pertussis toxin using Viaskin® | Mice | (73) | |
| Fractional ER:YAG (P.L.E.A.S.E. device) | 2940 nm | The limited inflammatory response induced by laser microporation activates DC | TH1/TH17-biased Ab and T cell responses using pollen allergen-mannan neoglycoconjugates | Mice, human skin explant (no immunogenicity study) | (80) | |
| Fractional ER:YAG (P.L.E.A.S.E. device) | 2940 nm | Suppressing allergenic responses if AFL and TH1-chemical adjuvant are combined in immunotherapy for pre-sensitized mice | Suppressed allergenic IgE and T cell responses to the grass pollen allergen Phl p 5 with CpG-ODN | Mice | (77) | |
| Fractional ER:YAG (P.L.E.A.S.E. device) | 2940 nm | Efficient antigen delivery to distinct APC population in the skin | TH2-biased Ab and T cell responses to model vaccines with CpG-ODN | Mice, Pig ear skin preparation (no immunogenicity study) | (62) | |
| Fractional ER:YAG (P.L.E.A.S.E. device) | 2940 nm | n.d. | Ab responses against HBsAg is dependent on a laser parameter and adjuvant to be combined | Mice | (64) | |
| Fractional ER:YAG (P.L.E.A.S.E. device) | 2940 nm | Increasing cytokine expression for TH1/Treg induction while suppressing TH2 response. | Enhanced Tregs, suppressed IgE response against OVA in combination with chemical adjuvants | Mice | (79) | |
| Fractional ER:YAG (P.L.E.A.S.E. device) | 2940 nm | Increasing cytokine expression | The resultant immune responses were largely not affected by the presence of γδ T cells or MCs. | Mice | (81) |
Ab, antibody; APC, antigen presenting cell; ATRA, all-trans retinoic acid; CpG-ODN, CpG-oligodeoxynucleotides; CW, continuous wave; CTLs, cytotoxic T lymphocytes; DC, dendritic cell; DAMPs, damage-associated molecular patterns, ER:YAG, erbium:yttrium-aluminium-garnet; MCs, mast cells; MTZ, microthermal zone; Nd:YAG, neodymium-doped yttrium aluminum garnet; Nd:YVO4, neodymium-doped yttrium orthovanadate; n.d., Not described; KTP, potassium titanyl phosphate; SCC, squamous cell carcinoma; TEM, effector memory; TRM, tissue-resident.