Increased CD56 expression after photodynamic therapy indicates an increased natural killer cell count following early photodynamic therapy for cutaneous squamous cell carcinoma

Zhao,Hongqing; Ren,Yuan; Kou,Huiling; Zhang,Junbo; Zhang,Xingcun

doi:10.3892/ol.2024.14505

Increased CD56 expression after photodynamic therapy indicates an increased natural killer cell count following early photodynamic therapy for cutaneous squamous cell carcinoma

Authors:
- Hongqing Zhao
- Yuan Ren
- Huiling Kou
- Junbo Zhang
- Xingcun Zhang
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Affiliations: Department of Plastic and Cosmetic Surgery, Daping Hospital, Army Medical University, Chongqing 400042, P.R. China, Department of Plastic and Cosmetic Surgery, Daping Hospital, Army Medical University, Chongqing 400042, P.R. China
Published online on: June 13, 2024 https://doi.org/10.3892/ol.2024.14505
Article Number: 372
Copyright: © Zhao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Cutaneous squamous cell carcinoma (cSCC) is the second most common type of skin cancer. Photodynamic therapy (PDT) is a promising therapeutic method for managing cSCC due to its proven ability to target specific areas over time and its low risk of side effects. PDT may cause tissue damage and vascular shutdown, and may regulate local immunological responses. The present study aimed to investigate and compare the early lymphocyte modifications before and after PDT for SCC. A total of 10 patients with SCC were identified by pathological investigation. Initially, all wounds were treated with 20% aminolevulinic acid (ALA)‑PDT as the initial stage in the therapeutic procedure. The wounds were treated by exposing them to red LED light with a wavelength of 635 nm, an energy density of 100 J/cm² and an intensity of 80 mW/cm². The tumor tissue was surgically removed 24 h later, and another round of PDT therapy was administered. Immunohistochemistry for CD3 and CD56 was conducted on the wound tissue post‑surgery. If the wound showed granulation, necrosis or secretion, debridement was added to the therapy. All patients were monitored for 0.6‑1.0 year post‑treatment. ALA‑PDT combination surgery fully controlled the tumor tissue in all 10 patients. The immunohistochemical analysis of the wound tissues showed that the expression of CD56 increased, while the expression of CD3 was not different after photodynamic therapy. These results also indirectly indicated that the overall count of NK cells in the 10 patients increased, nevertheless, there was no alteration in the T lymphocyte count. In conclusion, the ALA‑PDT combination surgical therapy for cSCC demonstrates favorable results. An increase in CD56 expression may be a mechanism for the effective treatment of cSCC with PDT.

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1	Gallego-Rentero M, Gutiérrez-Pérez M, Fernández-Guarino M, Mascaraque M, Portillo-Esnaola M, Gilaberte Y, Carrasco E and Juarranz Á: TGFβ1 secreted by cancer-associated fibroblasts as an inductor of resistance to photodynamic therapy in squamous cell carcinoma cells. Cancers (Basel). 13:56132021. View Article : Google Scholar : PubMed/NCBI
2	Hao Y, Chen Y, He X, Yang F, Han R, Yang C, Li W and Qian Z: Near-infrared responsive 5-fluorouracil and indocyanine green loaded MPEG-PCL nanoparticle integrated with dissolvable microneedle for skin cancer therapy. Bioact Mater. 5:542–552. 2020.PubMed/NCBI
3	Que SKT, Zwald FO and Schmults CD: Cutaneous squamous cell carcinoma: Incidence, risk factors, diagnosis, and staging. J Am Acad Dermatol. 78:237–247. 2018. View Article : Google Scholar : PubMed/NCBI
4	Martincorena I, Roshan A, Gerstung M, Ellis P, van Loo P, McLaren S, Wedge DC, Fullam A, Alexandrov LB, Tubio JM, et al: Tumor evolution. High burden and pervasive positive selection of somatic mutations in normal human skin. Science. 348:880–886. 2015. View Article : Google Scholar : PubMed/NCBI
5	Skulsky SL, O'Sullivan B, McArdle O, Leader M, Roche M, Conlon PJ and O'Neill JP: Review of high-risk features of cutaneous squamous cell carcinoma and discrepancies between the American Joint Committee on Cancer and NCCN Clinical Practice Guidelines In Oncology. Head Neck. 39:578–594. 2017. View Article : Google Scholar : PubMed/NCBI
6	Work Group and Invited Reviewers, . Kim JYS, Kozlow JH, Mittal B, Moyer J, Olenecki T and Rodgers P: Guidelines of care for the management of cutaneous squamous cell carcinoma. J Am Acad Dermatol. 78:560–578. 2018. View Article : Google Scholar : PubMed/NCBI
7	Xiang F, Lucas R, Hales S and Neale R: Incidence of nonmelanoma skin cancer in relation to ambient UV radiation in white populations, 1978–2012: Empirical relationships. JAMA Dermatol. 150:1063–1071. 2014. View Article : Google Scholar : PubMed/NCBI
8	Marsidi N, Ottevanger R, Bouwes Bavinck JN, Krekel-Taminiau NMA, Goeman JJ and Genders RE: Risk factors for incomplete excision of cutaneous squamous cell carcinoma: A large cohort study. J Eur Acad Dermatol Venereol. 36:1229–1234. 2022. View Article : Google Scholar : PubMed/NCBI
9	Curiel-Lewandrowski C, Myrdal CN, Saboda K, Hu C, Arzberger E, Pellacani G, Legat FJ, Ulrich M, Hochfellner P, Oliviero MC, et al: In Vivo reflectance confocal microscopy as a response monitoring tool for actinic keratoses undergoing cryotherapy and photodynamic therapy. Cancers (Basel). 13:54882021. View Article : Google Scholar : PubMed/NCBI
10	Keyal U, Bhatta AK, Zhang G and Wang XL: Present and future perspectives of photodynamic therapy for cutaneous squamous cell carcinoma. J Am Acad Dermatol. 80:765–773. 2019. View Article : Google Scholar : PubMed/NCBI
11	Wang XL, Wang HW, Guo MX and Xu SZ: T reatment of skin cancer and pre-cancer using topical ALA-PDT -a single hospital experience. Photodiagnosis Photodyn. Ther. 5:127–133. 2008.
12	Jaworski S, Biniecka P, Bugajska Ż, Daniluk K, Dyjak S, Strojny B, Kutwin M, Wierzbicki M, Grodzik M and Chwalibog A: Analysis of the cytotoxicity of hierarchical nanoporous graphenic carbon against human glioblastoma grade IV cells. Int J Nanomedicine. 12:3839–3849. 2017. View Article : Google Scholar : PubMed/NCBI
13	Wilson C, Zhang X, Buckley C, Heathcote HR, Lee MD and McCarron JG: Increased vascular contractility in hypertension results from impaired endothelial calcium signaling. Hypertension. 74:1200–1214. 2019. View Article : Google Scholar : PubMed/NCBI
14	Castano AP, Mroz P and Hamblin MR: Photodynamic therapy and anti-tumour immunity. Nat Rev Cancer. 6:535–545. 2006. View Article : Google Scholar : PubMed/NCBI
15	Wang X, Ji J, Zhang H, Fan Z, Zhang L, Shi L, Zhou F, Chen WR, Wang H and Wang X: Stimulation of dendritic cells by DAMPs in ALA-PDT treated SCC tumor cells. Oncotarget. 6:44688–44702. 2015. View Article : Google Scholar : PubMed/NCBI
16	Wang H, Li J, Lv T, Tu Q, Huang Z and Wang X: Therapeutic and immune effects of 5-aminolevulinic acid photodynamic therapy on UVB-induced squamous cell carcinomas in hairless mice. Exp Dermatol. 22:362–363. 2013. View Article : Google Scholar : PubMed/NCBI
17	Nakaseko H, Kobayashi M, Akita Y, Tamada Y and Matsumoto Y: Histological changes and involvement of apoptosis after photodynamic therapy for actinic keratosis. Br J Dermatol. 148:122–127. 2003. View Article : Google Scholar : PubMed/NCBI
18	Gellén E, Fidrus E, Péter M, Szegedi A, Emri G and Remenyik É: Immunological effects of photodynamic therapy in the treatment of actinic keratosis and squamous cell carcinoma. Photodiagnosis Photodyn Ther. 24:342–348. 2018. View Article : Google Scholar : PubMed/NCBI
19	Souwer IH, Bor JH, Smits P and Lagro-Janssen AL: Nifedipine vs placebo for treatment of chronic chilblains: A randomized controlled trial. Ann Fam Med. 14:453–459. 2016. View Article : Google Scholar : PubMed/NCBI
20	Zou F, Lu L, Liu J, Xia B, Zhang W, Hu Q, Liu W, Zhang Y, Lin Y, Jing S, et al: Engineered triple inhibitory receptor resistance improves anti-tumor CAR-T cell performance via CD56. Nat Commun. 10:41092019. View Article : Google Scholar : PubMed/NCBI
21	Tang X, Qin Y, Sheng X, Xing J and Zhan W: Characterization of CD3+ T lymphocytes of Japanese flounder (Paralichthys olivaceus) and its response after immunization with formalin-inactivated Edwardsiella tarda. Fish Shellfish Immunol. 63:220–227. 2017. View Article : Google Scholar : PubMed/NCBI
22	Gleich T, Chiticariu E, Huber M and Hohl D: Keratoacan-thoma: A distinct entity? Exp Dermatol. 25:85–91. 2016. View Article : Google Scholar : PubMed/NCBI
23	Kwiek B and Schwartz RA: Keratoacanthoma (KA): An update and review. J Am Acad Dermatol. 74:1220–1233. 2016. View Article : Google Scholar : PubMed/NCBI
24	Selmer J, Skov T, Spelman L and Weedon D: Squamous cell carcinoma and keratoacanthomas are biologically distinct and can be diagnosed by light microscopy: A review. Histopathology. 69:535–541. 2016. View Article : Google Scholar : PubMed/NCBI
25	Cassarino DS, Derienzo DP and Barr RJ: Cutaneous squamous cell carcinoma: A comprehensive clinicopathologic classification-part two. J Cutan Pathol. 33:261–279. 2006. View Article : Google Scholar : PubMed/NCBI
26	Hao Y, Gu Z, Yu Z, Schomann T, Sayedipour S, Aguilar JC, Ten Dijke P and Cruz LJ: Photodynamic therapy in combination with the hepatitis B core virus-like particles (HBc VLPs) to prime anticancer immunity for colorectal cancer treatment. Cancers (Basel). 14:27242022. View Article : Google Scholar : PubMed/NCBI
27	Mossakowska BJ, Shahmoradi Ghahe S, Cysewski D, Fabisiewicz A, Tudek B and Siedlecki JA: Mechanisms of resistance to photodynamic therapy (PDT) in vulvar cancer. Int J Mol Sci. 23:41172022. View Article : Google Scholar : PubMed/NCBI
28	Yang Z, Hu X, Zhou L, He Y, Zhang X, Yang J, Ju Z, Liou YC, Shen HM, Luo G, et al: Photodynamic therapy accelerates skin wound healing through promoting re-epithelialization. Burns Trauma. 9:tkab0082021. View Article : Google Scholar : PubMed/NCBI
29	Yang Y, Wang C, Zhuge Y, Zhang J, Xu K, Zhang Q, Zhang H, Chen H, Chu M and Jia C: Photodynamic antifungal activity of hypocrellin a against candida albicans. Front Microbiol. 10:18102019. View Article : Google Scholar : PubMed/NCBI
30	Zhang J, Zhao T, Han F, Hu Y and Li Y: Photothermal and gene therapy combined with immunotherapy to gastric cancer by the gold nanoshell-based system. J Nanobiotechnology. 17:802019. View Article : Google Scholar : PubMed/NCBI
31	Zhang Q, Wu B, Weng Q, Hu F, Lin Y, Xia C, Peng H, Wang Y, Liu X, Liu L, et al: Regeneration of immunocompetent B lymphopoiesis from pluripotent stem cells guided by transcription factors. Cell Mol Immunol. 19:492–503. 2022. View Article : Google Scholar : PubMed/NCBI
32	Algarin YA, Jambusaria-Pahlajani A, Ruiz E and Patel VA: Advances in topical treatments of cutaneous malignancies. Am J Clin Dermatol. 24:69–80. 2023. View Article : Google Scholar : PubMed/NCBI
33	Zhao H, Sun J and Yang Y: Research progress of photodynamic therapy in wound healing: A literature review. J Burn Care Res. 44:1327–1333. 2023. View Article : Google Scholar : PubMed/NCBI
34	Zhao Z, Wu Y, Zhou Z, Zhao Y, Sun X, Hu C, Wang X and Zhang G: ALA-PDT successfully treated multiple cSCC in situ and AK in a patient with Epidermodysplasia verruciformis. Photodiagnosis Photodyn Ther. 35:1023952021. View Article : Google Scholar : PubMed/NCBI
35	Aggarwal I, Puyana C, Chandan N, Jetter N and Tsoukas M: Field cancerization therapies for the management of actinic keratosis: An updated review. Am J Clin Dermatol. 25:391–405. 2024. View Article : Google Scholar : PubMed/NCBI
36	Heipertz EL, Zynda ER, Stav-Noraas TE, Hungler AD, Boucher SE, Kaur N and Vemuri MC: Current perspectives on ‘Off-The-Shelf’ allogeneic NK and CAR-NK cell therapies. Front Immunol. 12:7321352021. View Article : Google Scholar : PubMed/NCBI
37	Morvan MG and Lanier LL: NK cells and cancer: You can teach innate cells new tricks. Nat Rev Cancer. 16:7–19. 2016. View Article : Google Scholar : PubMed/NCBI
38	Bryceson YT, March ME, Barber DF, Ljunggren HG and Long EO: Cytolytic granule polarization and degranulation controlled by different receptors in resting NK cells. J Exp Med. 202:1001–1012. 2005. View Article : Google Scholar : PubMed/NCBI
39	Gonçalves-Maia M, Gache Y, Basante M, Cosson E, Salavagione E, Muller M, Bernerd F, Avril MF, Schaub S, Sarasin A, et al: NK cell and Fibroblast-Mediated regulation of skin squamous cell carcinoma invasion by CLEC2A is compromised in Xeroderma pigmentosum. J Invest Dermatol. 140:1723–1732. 2020. View Article : Google Scholar : PubMed/NCBI
40	Ortner D, Tripp CH, Komenda K, Dubrac S, Zelger B, Hermann M, Doppler W, Tymoszuk PZ, Boon L, Clausen BE and Stoitzner P: Langerhans cells and NK cells cooperate in the inhibition of chemical skin carcinogenesis. Oncoimmunology. 6:e12602152016. View Article : Google Scholar : PubMed/NCBI
41	Chen X, Chen X, Gao J, Yang H, Duan Y, Feng Y, He X, Gong X, Wang H, Wu X and Chang J: Astragaloside III enhances anti-tumor response of NK cells by elevating NKG2D and IFN-γ. Front Pharmacol. 10:8982019. View Article : Google Scholar : PubMed/NCBI
42	Shi J, Wu P, Sheng L, Sun W and Zhang H: Ferroptosis-related gene signature predicts the prognosis of papillary thyroid carcinoma. Cancer Cell Int. 21:6692021. View Article : Google Scholar : PubMed/NCBI
43	Gill S, Vasey AE, De Souza A, Baker J, Smith AT, Kohrt HE, Florek M, Gibbs KD Jr, Tate K, Ritchie DS and Negrin RS: Rapid development of exhaustion and down-regulation of eomesodermin limit the antitumor activity of adoptively transferred murine natural killer cells. Blood. 119:5758–5768. 2012. View Article : Google Scholar : PubMed/NCBI
44	Oyer JL, Gitto SB, Altomare DA and Copik AJ: PD-L1 blockade enhances anti-tumor efficacy of NK cells. Oncoimmunology. 7:e15098192018. View Article : Google Scholar : PubMed/NCBI
45	Luci C, Bihl F, Bourdely P, Khou S, Popa A, Meghraoui-Kheddar A, Vermeulen O, Elaldi R, Poissonnet G, Sudaka A, et al: Cutaneous squamous cell carcinoma development is associated with a temporal infiltration of ILC1 and NK cells with immune dysfunctions. J Invest Dermatol. 141:2369–2379. 2021. View Article : Google Scholar : PubMed/NCBI
46	Fu XQ, Liu B, Wang YP, Li JK, Zhu PL, Li T, Tse KW, Chou JY, Yin CL, Bai JXL, et al: Activation of STAT3 is a key event in TLR4 signaling-mediated melanoma progression. Cell Death Dis. 11:2462020. View Article : Google Scholar : PubMed/NCBI
47	Vuong NL, Cheung KW, Periaswamy B, Vi TT, Duyen HTL, Leong YS, Binte Hamis ZN, Gregorova M, Ooi EE, Sessions O, et al: Hyperinflammatory syndrome, natural killer cell function, and genetic polymorphisms in the pathogenesis of severe dengue. J Infect Dis. 226:1338–1347. 2022. View Article : Google Scholar : PubMed/NCBI