Unlocking the role of tumor-associated macrophages (TAMs) in feline injection-site sarcomas – a path to immunotherapy

Helena Gomes , Rita Files , Gabriela Maia , Ana Vidal , Maria Silva , Justina Prada , Isabel Pires , Filipe Silva

Animal Diseases ›› 2025, Vol. 5 ›› Issue (1) : 11

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Animal Diseases ›› 2025, Vol. 5 ›› Issue (1) : 11 DOI: 10.1186/s44149-025-00165-y
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Unlocking the role of tumor-associated macrophages (TAMs) in feline injection-site sarcomas – a path to immunotherapy

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Abstract

Feline injection site sarcomas (FISSs) are tumors frequently found at injection sites in domestic cats associated with vaccines and other pharmaceutical substances. The most accepted theory suggests that chronic inflammatory reactions at the injection site trigger these tumors. This study analyzed 58 cases of FISS in cats to investigate the role of tumor-associated macrophages (TAMs). Immunohistochemistry for MAC387+ macrophages was performed via the Novolink™ polymer detection system. TAMs were quantified and categorized into low, moderate, and extensive infiltration groups. Most tumors showed sparse macrophage infiltration (29 out of 58 cases), with moderate macrophage infiltration (18 out of 58), and 11 cases out of 58 showed high infiltration. Significant associations were found between TAM infiltration and the degree of differentiation (p<0.001), degree of necrosis (p=0.033), mitotic index (p= 0.003), and histological degree of malignancy (p<0.001). This study revealed that TAM density is correlated with tumor aggressiveness in the FISS, suggesting a fundamental role for macrophages in the tumor microenvironment and a promising marker for prognosis.

Keywords

Feline injection-site sarcomas / Tumor-associated macrophages / Feline / Vaccine

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Helena Gomes, Rita Files, Gabriela Maia, Ana Vidal, Maria Silva, Justina Prada, Isabel Pires, Filipe Silva. Unlocking the role of tumor-associated macrophages (TAMs) in feline injection-site sarcomas – a path to immunotherapy. Animal Diseases, 2025, 5(1): 11 DOI:10.1186/s44149-025-00165-y

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References

[1]

ArnethB. Tumor Microenvironment. Medicina, 2019, 56115.

[2]

BradyRV, ThammDH. Tumor-associated macrophages: Prognostic and therapeutic targets for cancer in humans and dogs. Frontiers in Immunology, 2023, 14: 1176807.

[3]

CarneiroCS, De QueirozGF, PintoAC, DagliML, MateraJM. Feline injection site sarcoma: Immunohistochemical characteristics. Journal of Feline Medicine and Surgery, 2019, 214314-321.

[4]

CeccoBS, HenkerLC, De LorenzoC, SchwertzCI, BianchiRM, Da CostaFVA, et al. . Epidemiological and pathological characterization of feline injection site sarcomas in Southern Brazil. Journal of Comparative Pathology, 2019, 172: 31-36.

[5]

ChenD, ZhangX, LiZ, ZhuB. Metabolic regulatory crosstalk between tumor microenvironment and tumor-associated macrophages. Theranostics, 2021, 1131016-1030.

[6]

CoutoSS, GriffeySM, DuartePC, MadewellBR. Feline vaccine-associated fibrosarcoma: Morphologic distinctions. Veterinary Pathology, 2002, 39133-41.

[7]

DayRM, HaoX, IlyasM, DaszakP, TalbotIC, ForbesA. Changes in the expression of syndecan-1 in the colorectal adenoma-carcinoma sequence. Virchows Archiv, 1999, 4342121-125.

[8]

DobromylskyjM. Feline soft tissue sarcomas: A review of the classification and histological grading, with comparison to human and canine. Animals, 2022, 12202736.

[9]

FilesR, OkwuV, TopaN, SousaM, SilvaF, RodriguesP, DelgadoL, PradaJ, PiresI. Assessment of tumor-associated tissue eosinophilia (TATE) and tumor-associated macrophages (TAMs) in canine transitional cell carcinoma of the Urinary Bladder. Animals, 2024, 143519.

[10]

GanjooKN, WittenD, PatelM, EspinosaI, LaT, TibshiraniR, et al. . The prognostic value of tumor-associated macrophages in Leiomyosarcoma: A single institution study. American Journal of Clinical Oncology, 2011, 34182-86.

[11]

HartmannK, DayMJ, ThiryE, LloretA, FrymusT, AddieD, et al. . Feline injection-site sarcoma: ABCD guidelines on prevention and management. Journal of Feline Medicine and Surgery, 2015, 177606-613.

[12]

HartmannK, EgberinkH, MöstlK, AddieDD, BelákS, Boucraut-BaralonC, et al. . Feline injection-site sarcoma and other adverse reactions to vaccination in cats. Viruses, 2023, 1581708.

[13]

HauckM. Feline injection site sarcomas. Veterinary Clinics of North America: Small Animal Practice, 2003, 333553-571.

[14]

KassPH, SpanglerWL, HendrickMJ, McGillLD, EsplinDG, LesterS, et al. . Multicenter case-control study of risk factors associated with development of vaccine-associated sarcomas in cats. Journal of the American Veterinary Medical Association, 2003, 22391283-1292.

[15]

KirpensteijnJ. Feline injection site-associated sarcoma: Is it a reason to critically evaluate our vaccination policies?. Veterinary Microbiology, 2006, 117159-65.

[16]

Lopez-BeltranA, RequenaMJ, Alvarez-KindelanJ, QuinteroA, BlancaA, MontironiR. Squamous differentiation in primary urothelial carcinoma of the urinary tract as seen by MAC387 immunohistochemistry. Journal of Clinical Pathology, 2007, 603332-335.

[17]

MartanoM, MorelloE, BuraccoP. Feline injection-site sarcoma: Past, present and future perspectives. The Veterinary Journal, 2011, 1882136-141.

[18]

MartanoM, MorelloE, AvnetS, CostaF, SammartanoF, KusuzakiK, et al. . Photodynamic surgery for feline injection-site sarcoma. BioMed Research International, 2019, 2019: 1-9.

[19]

MonteiroLN, Dos ReisDC, SalgadoBS, CassaliGD. Clinical significance and prognostic role of tumor-associated macrophages infiltration according to histologic location in canine mammary carcinomas. Research in Veterinary Science, 2021, 135: 329-334.

[20]

NascimentoC, GameiroA, CorreiaJ, FerreiraJ, FerreiraF. The landscape of tumor-infiltrating immune cells in feline mammary carcinoma: Pathological and clinical implications. Cells, 2022, 11162578.

[21]

PinelloK, PiresI, CastroAF, CarvalhoPT, SantosA, De MatosA, et al. . Cross species analysis and comparison of tumors in dogs and cats, by age, sex, topography and main morphologies. Data from Vet-OncoNet. Veterinary Sciences, 2022, 94167.

[22]

PorcellatoI, MenchettiL, BrachelenteC, SfornaM, ReginatoA, LepriE. Feline injection-site sarcoma: Matrix remodeling and prognosis. Veterinary Pathology, 2017, 542204-211.

[23]

RomanelliG, MarconatoL, OliveroD, MassariF, ZiniE. Analysis of prognostic factors associated with injection-site sarcomas in cats: 57 cases (2001–2007). Journal of the American Veterinary Medical Association, 2008, 23281193-1199.

[24]

SéguinB. Injection site sarcomas in cats. Clinical Techniques in Small Animal Practice, 2002, 174168-173.

[25]

VitaleI, ManicG, CoussensLM, KroemerG, GalluzziL. Macrophages and metabolism in the tumor microenvironment. Cell Metabolism, 2019, 30136-50.

[26]

WuH, ZhangX, HanD, CaoJ, TianJ. Tumor-associated macrophages mediate the invasion and metastasis of bladder cancer cells through CXCL8. PeerJ, 2020, 8. e8721

[27]

XiangX, WangJ, LuD, XuX. Targeting tumor-associated macrophages to synergize tumor immunotherapy. Signal Transduction and Targeted Therapy, 2021, 6175.

[28]

XiaoY, YuD. Tumor microenvironment as a therapeutic target in cancer. Pharmacology & Therapeutics, 2021, 221. 107753

[29]

YanS, WanG. Tumor-associated macrophages in immunotherapy. The FEBS Journal, 2021, 288216174-6186.

[30]

Zabielska-KoczywąsK, WojtalewiczA, LechowskiR. Current knowledge on feline injection-site sarcoma treatment. Acta Veterinaria Scandinavica, 2017, 59147.

[31]

ZhangQ, SioudM. Tumor-associated macrophage subsets: Shaping polarization and targeting. International Journal of Molecular Sciences, 2023, 2487493.

[32]

ZhangH, LiuL, LiuJ, DangP, HuS, YuanW, et al. . Roles of tumor-associated macrophages in anti-PD-1/PD-L1 immunotherapy for solid cancers. Molecular Cancer, 2023, 22158.

Funding

This research was funded by the Portuguese Foundation for Science and Technology (FCT), sup-ported by the projects UIDB/00772/2020 (https://doi.org/10.54499/UIDB/00772/2020).(This research was funded by the Portuguese Foundation for Science)

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