# The immune microenvironment in endometrial carcinoma: mechanisms and therapeutic targeting

**Authors:** Yilin Wang, Nana Liu, Xiangcui Guo, Ruobing Han, Jin Bai, Jiateng Zhong, Qianqing Wang

PMC · DOI: 10.3389/fimmu.2025.1586315 · Frontiers in Immunology · 2025-07-17

## TL;DR

This paper reviews how the immune environment in endometrial cancer affects tumor growth and treatment resistance, and explores new therapies targeting this environment.

## Contribution

The paper provides a comprehensive review of the tumor immune microenvironment in endometrial carcinoma and novel therapeutic strategies targeting it.

## Key findings

- The tumor immune microenvironment influences endometrial cancer progression and resistance to treatment.
- Components like TAMs, MDSCs, and CAFs contribute to an immunosuppressive environment.
- Therapies targeting immune checkpoints and extracellular vesicles show promise for improving patient outcomes.

## Abstract

Endometrial carcinoma (EC) represents one of the most prevalent malignancies within the female reproductive system. The frequency of its occurrence is on the rise annually, and patients diagnosed at advanced stages face a less favorable prognosis. Recent studies have highlighted the significant influence of the tumor immune microenvironment (TME) on the initiation, progression, metastasis, and therapeutic resistance of endometrial cancer. The TME encompasses various components such as tumor-associated macrophages (TAMs), myeloid-derived suppressor cells (MDSCs), cancer-associated fibroblasts (CAFs), immune cells, and the extracellular matrix (ECM). These elements contribute to an immunosuppressive milieu by secreting cytokines, extracellular vesicles (EVs), and engaging immune checkpoint pathways like PD-1/PD-L1, thereby supporting tumor immune evasion and resistance to treatment. This review synthesizes current understanding of the EC-TME, focusing on the distinct roles and interactions of its key constituents within the context of EC biology. Furthermore, we explore the rationale and progress for novel therapeutic strategies targeting the TME, such as immune checkpoint inhibitors, combination therapies, and nano delivery systems leveraging EVs, aiming to provide insights for improving EC patient outcomes.

## Linked entities

- **Diseases:** endometrial carcinoma (MONDO:0002447), endometrial cancer (MONDO:0002447)

## Full-text entities

- **Genes:** NOS2 (nitric oxide synthase 2) [NCBI Gene 4843] {aka HEP-NOS, INOS, NOS, NOS2A}, LOX (lysyl oxidase) [NCBI Gene 4015] {aka AAT10}, IL13 (interleukin 13) [NCBI Gene 3596] {aka IL-13, P600}, TGFB1 (transforming growth factor beta 1) [NCBI Gene 7040] {aka CAEND1, CED, DPD1, IBDIMDE, LAP, TGF-beta1}, CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}, MIR223 (microRNA 223) [NCBI Gene 407008] {aka MIRN223, miRNA223, mir-223}, PDCD1 (programmed cell death 1) [NCBI Gene 5133] {aka ADMIO4, AIMTBS, CD279, PD-1, PD1, SLEB2}, ABCB1 (ATP binding cassette subfamily B member 1) [NCBI Gene 5243] {aka ABC20, CD243, CLCS, ENPAT, GP170, MDR1}, AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, CXCR2 (C-X-C motif chemokine receptor 2) [NCBI Gene 3579] {aka CD182, CDw128b, CMKAR2, IL8R2, IL8RA, IL8RB}, IFNG (interferon gamma) [NCBI Gene 3458] {aka IFG, IFI, IMD69}, MTOR (mechanistic target of rapamycin kinase) [NCBI Gene 2475] {aka FRAP, FRAP1, FRAP2, RAFT1, RAPT1, SKS}, TAFAZZIN (tafazzin, phospholipid-lysophospholipid transacylase) [NCBI Gene 6901] {aka BTHS, CMD3A, EFE, EFE2, G4.5, LVNCX}, SRC (SRC proto-oncogene, non-receptor tyrosine kinase) [NCBI Gene 6714] {aka ASV, SRC1, THC6, c-SRC, p60-Src}, TLR4 (toll like receptor 4) [NCBI Gene 7099] {aka ARMD10, CD284, TLR-4, TOLL}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, IDO1 (indoleamine 2,3-dioxygenase 1) [NCBI Gene 3620] {aka IDO, IDO-1, INDO}, PIK3CB (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta) [NCBI Gene 5291] {aka P110BETA, PI3K, PI3KBETA, PIK3C1}, CSF1R (colony stimulating factor 1 receptor) [NCBI Gene 1436] {aka BANDDOS, C-FMS, CD115, CSF-1R, CSFR, FIM2}, VEGFA (vascular endothelial growth factor A) [NCBI Gene 7422] {aka L-VEGF, MVCD1, VEGF, VPF}, IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}, IL10 (interleukin 10) [NCBI Gene 3586] {aka CSIF, GVHDS, IL-10, IL10A, TGIF}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, CXCL8 (C-X-C motif chemokine ligand 8) [NCBI Gene 3576] {aka GCP-1, GCP1, IL8, LECT, LUCT, LYNAP}, FAP (fibroblast activation protein alpha) [NCBI Gene 2191] {aka DPPIV, FAPA, FAPalpha, SIMP}, PGP (phosphoglycolate phosphatase) [NCBI Gene 283871] {aka AUM, G3PP, PGPase}, SMPD2 (sphingomyelin phosphodiesterase 2) [NCBI Gene 6610] {aka ISC1, NSMASE, NSMASE1}, CXCL12 (C-X-C motif chemokine ligand 12) [NCBI Gene 6387] {aka IRH, PBSF, SCYB12, SDF1, TLSF, TPAR1}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, PTK2 (protein tyrosine kinase 2) [NCBI Gene 5747] {aka FADK, FADK 1, FAK, FAK1, FRNK, PPP1R71}, PRAP1 (proline rich acidic protein 1) [NCBI Gene 118471] {aka PRO1195, UPA}, EGF (epidermal growth factor) [NCBI Gene 1950] {aka HOMG4, URG}, CD274 (CD274 molecule) [NCBI Gene 29126] {aka ADMIO5, B7-H, B7H1, PD-L1, PDCD1L1, PDCD1LG1}, NELFCD (negative elongation factor complex member C/D) [NCBI Gene 51497] {aka HSPC130, NELF-C, NELF-D, TH1, TH1L}, ARG1 (arginase 1) [NCBI Gene 383], YAP1 (Yes1 associated transcriptional regulator) [NCBI Gene 10413] {aka COB1, YAP, YAP-1, YAP2, YAP65, YKI}, HGF (hepatocyte growth factor) [NCBI Gene 3082] {aka DFNB39, F-TCF, HGFB, HPTA, SF}, IL12B (interleukin 12B) [NCBI Gene 3593] {aka CLMF, CLMF2, IL-12B, IMD28, IMD29, NKSF}, IL4 (interleukin 4) [NCBI Gene 3565] {aka BCGF-1, BCGF1, BSF-1, BSF1, IL-4}, CD247 (CD247 molecule) [NCBI Gene 919] {aka CD3-ZETA, CD3H, CD3Q, CD3Z, CD3ZETA, IMD25}, STAT3 (signal transducer and activator of transcription 3) [NCBI Gene 6774] {aka ADMIO, ADMIO1, APRF, HIES}, TLR9 (toll like receptor 9) [NCBI Gene 54106] {aka CD289}, CD274 (CD274 molecule) [NCBI Gene 574058] {aka PDL1}
- **Diseases:** hypoxic (MESH:D002534), MDSCs (OMIM:601308), tumorigenic (MESH:D002471), cytotoxic (MESH:D064420), EC (MESH:D016889), hypoxia (MESH:D000860), metastasis (MESH:D009362), MSS (MESH:D053842), Cancer (MESH:D009369), inflammation (MESH:D007249), MDR (MESH:D018088), inflammatory cytokines (MESH:D000080424)
- **Chemicals:** GSH (MESH:D005978), ATRA (MESH:D014212), NO (MESH:D009569), ornithine (MESH:D009952), pentose phosphate (MESH:D010428), Bevacizumab (MESH:D000068258), BioRender (-), RNS (MESH:D011886), platinum (MESH:D010984), oxygen (MESH:D010100), cysteine (MESH:D003545), L-arginine (MESH:D001120), cisplatin (MESH:D002945), lipid (MESH:D008055), heparin (MESH:D006493), ROS (MESH:D017382), tryptophan (MESH:D014364), polyamines (MESH:D011073), Lactic acid (MESH:D019344), fatty acid (MESH:D005227)
- **Species:** Homo sapiens (human, species) [taxon 9606], Enterovirus C (no rank) [taxon 138950]

## Full text

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## References

82 references — full list in the complete paper: https://tomesphere.com/paper/PMC12310473/full.md

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Source: https://tomesphere.com/paper/PMC12310473