Research progress on immune microenvironment and immunotherapy of endometrial cancer

doi:10.3969/j.issn.1674-8115.2026.05.012

Abstract

Abstract:

Endometrial carcinoma (EC) is a common malignant tumor that poses a severe threat to women's health. Driven by an aging population and the high prevalence of metabolic diseases, the incidence of EC continues to rise. For advanced or recurrent EC, traditional therapeutic regimens exhibit limited efficacy and are prone to drug resistance, leading to a generally poor overall prognosis. To overcome this clinical bottleneck, immunotherapeutic strategies, characterized by high targeting specificity and durable efficacy, have opened up a novel direction for clinical treatment. This review systematically summarizes the cellular composition and molecular subtyping characteristics of the EC immune microenvironment, and elaborates on the research progress of immune checkpoint inhibitors (ICIs) in monotherapy and combination regimens. Furthermore, it provides an in-depth analysis of current challenges, including efficacy heterogeneity and drug resistance, to provide a reference for the clinical practice and theoretical research of precision immunotherapy for EC.

Key words: immune microenvironment, immune checkpoint inhibitor (ICI), endometrial carcinoma (EC), immunotherapy

CLC Number:

R737.33

Chen Yuhan, Ai Zhihong. Research progress on immune microenvironment and immunotherapy of endometrial cancer[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2026, 46(5): 656-664.

Figures/Tables 3

TrendMD

References 62

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Drug	Study	Phase	Sample size/n	Biomarker	Primary endpoint	Secondary endpoint	ORR (95% CI)	mDOR(95% CI)	mPFS (95% CI)	mOS (95% CI)
Pembrolizumab	KEYNOTE-028^[35](NCT02054806)	Phase Ⅰb	75	PD-L1, MSI	ORR	Safety, DOR, PFS, OS	13.0 (2.8‒33.6)	NR	1.8 (1.6‒2.7)	NR
Pembrolizumab	KEYNOTE-158^[29-30](NCT02628067)	Phase Ⅱ	90 (Cohort D for EC: 11; Cohort K for non-colorectal MSI-H/dMMR solid tumors: 79)	MMR/MSI, PD-L1	ORR	DOR, PFS, OS, Safety	48 (37‒60)	NR	13.1 (4.3‒34.4)	NR
Avelumab	NCT02912572^[31]	Phase Ⅱ	33	MMR, POLE ultramutated, TMB	OR, PFS6	PFS, OS, Safety	dMMR: 26.7 (7.8‒55.1); pMMR/non-POLE: 6.25 (0.16‒30.2)	NA	dMMR: 4.4 (1.7‒NR); pMMR/non-POLE: 1.9 (1.6‒2.8)	dMMR: NR pMMR/non-POLE: 6.6 (2.0‒10.2)
Durvalumab	ANZGOG1601, ACTRN12617000106336^[32] (NCT03015129)	Phase Ⅱ	dMMR: 36; pMMR: 35	MMR	OTR	OTR, PFS, OS, AEs, HRQL, etc.	dMMR: 47 (32‒63); pMMR: 3 (1‒5)	NA	dMMR: 8.3 (2.4‒NR); pMMR: 1.8 (1.8‒2.0)	dMMR: NR pMMR: 12.1
Dostarlimab	GARNET^[33](NCT02715284)	Phase Ⅰ	327 (dMMR EC:141)	MMR/MSI, POLE ultramutated	ORR and DOR in patients with dMMR solid tumors	ORR and DOR in dMMR solid tumors in Cohorts A1 and F; individual PFS and OS for each cohort, etc.	45.5 (37.1‒54.0)	NR	6.0 (4.1‒18.0)	NR
Retifanlimab	POD1UM-101^[34](NCT03059823)	Phase Ⅰ	76	MMR/MSI, PD-L1	Safety, tolerability	ORR, DOR, PFS, OS	51.3 (39.6‒63.0)	NR	12.2 (6.0‒33.4)	30.2 (19.3‒NR)

Drug	Study	Phase	Sample size/n	Biomarker	Primary endpoint	Secondary endpoint	ORR (95% CI)	mDOR(95% CI)	mPFS (95% CI)	mOS (95% CI)
Pembrolizumab	KEYNOTE-028^[35](NCT02054806)	Phase Ⅰb	75	PD-L1, MSI	ORR	Safety, DOR, PFS, OS	13.0 (2.8‒33.6)	NR	1.8 (1.6‒2.7)	NR
Pembrolizumab	KEYNOTE-158^[29-30](NCT02628067)	Phase Ⅱ	90 (Cohort D for EC: 11; Cohort K for non-colorectal MSI-H/dMMR solid tumors: 79)	MMR/MSI, PD-L1	ORR	DOR, PFS, OS, Safety	48 (37‒60)	NR	13.1 (4.3‒34.4)	NR
Avelumab	NCT02912572^[31]	Phase Ⅱ	33	MMR, POLE ultramutated, TMB	OR, PFS6	PFS, OS, Safety	dMMR: 26.7 (7.8‒55.1); pMMR/non-POLE: 6.25 (0.16‒30.2)	NA	dMMR: 4.4 (1.7‒NR); pMMR/non-POLE: 1.9 (1.6‒2.8)	dMMR: NR pMMR/non-POLE: 6.6 (2.0‒10.2)
Durvalumab	ANZGOG1601, ACTRN12617000106336^[32] (NCT03015129)	Phase Ⅱ	dMMR: 36; pMMR: 35	MMR	OTR	OTR, PFS, OS, AEs, HRQL, etc.	dMMR: 47 (32‒63); pMMR: 3 (1‒5)	NA	dMMR: 8.3 (2.4‒NR); pMMR: 1.8 (1.8‒2.0)	dMMR: NR pMMR: 12.1
Dostarlimab	GARNET^[33](NCT02715284)	Phase Ⅰ	327 (dMMR EC:141)	MMR/MSI, POLE ultramutated	ORR and DOR in patients with dMMR solid tumors	ORR and DOR in dMMR solid tumors in Cohorts A1 and F; individual PFS and OS for each cohort, etc.	45.5 (37.1‒54.0)	NR	6.0 (4.1‒18.0)	NR
Retifanlimab	POD1UM-101^[34](NCT03059823)	Phase Ⅰ	76	MMR/MSI, PD-L1	Safety, tolerability	ORR, DOR, PFS, OS	51.3 (39.6‒63.0)	NR	12.2 (6.0‒33.4)	30.2 (19.3‒NR)

Study	Drug	Phase	Sample size/n	Biomarker	Primary endpoint	Secondary endpoint
NRG-GY018(KEYNOTE-868)^[41]	Pembrolizumab plus paclitaxel/carboplatin	Phase Ⅲ	dMMR: 225; pMMR: 591	MMR	PFS in patients with dMMR and pMMR	Safety, OS, and health-related quality of life
ENGOT-en11/GOG-3053(KEYNOTE-B21)^[42]	Pembrolizumab plus paclitaxel/carboplatin	Phase Ⅲ	dMMR: 281; pMMR: 814	MMR	DFS, OS	DFS, AEs, PROs
ENGOT-EN-6-NSGO/GOG-3031/RUBY^[43]	Dostarlimab plus paclitaxel/carboplatin	Phase Ⅲ	dMMR/MSI-H: 118; pMMR-MSS: 376	MSI/MMR	PFS in dMMR/MSI-H patients, overall PFS, and OS	PFS, ORR. DOR, etc.
DUO-E^[44]	Durvalumab/olaparib plus paclitaxel/carboplatin	Phase Ⅲ	718	MMR, PD-L1, HRRm	PFS	OS, safety, etc.
AtTEnd^[45]	Atezolizumab plus carboplatin/paclitaxel	Phase Ⅲ	551	MMR, PD-L1	PFS in dMMR patients and overall PFS and OS	ORR, DoR, PFS2, safety, etc.
KEYNOTE-146^[46-48]	Pembrolizumab plus lenvatinib	Phase Ⅰb /Ⅱ	108	MMR/MSI	ORR	ORR, DOR, PFS, OS, safety, etc.
KEYNOTE-775^[49-50]	Pembrolizumab plus lenvatinib	Phase Ⅲ	dMMR: 130; pMMR: 697	MMR	PFS and OS in patients with dMMR/pMMR	ORR
CAP 04^[51]	Camrelizumab plus apatinib	Phase Ⅰ	36	MMR/MSI, PD-L1	ORR	DCR, TTR, DOR, TTF, PFS, OS, safety, etc.
Study	mPFS and HR		PFS and HR			mOS and HR
NRG-GY018(KEYNOTE-868)^[41]	dMMR: NR vs 7.6 (HR: 0.30); pMMR: 13.1 vs 8.7 (HR: 0.54)		(12 months) dMMR: 74 vs 38 (HR: 0.30); pMMR: 13.1 vs 8.7 (HR: 0.54)			NA
ENGOT-en11/GOG-3053(KEYNOTE-B21)^[42]	NA		NA			NA
ENGOT-EN-6-NSGO/GOG-3031/RUBY^[43]	NA		(24 months) dMMR: 61.4 vs 15.7 (HR: 0.28); pMMR: 28.4 vs 18.8 (HR: 0.76); Overall: 36.1 vs 18.1 (HR: 0.64)			NA
DUO-E^[44]	CP+D+D, CP+D, and CP ITT: 15.1 vs 10.2 vs 9.6; dMMR: 31.8 vs NR vs 7.0; pMMR: 15.0 vs 9.9 vs 9.7		NA			CP+D+D, CP+D, and CP ITT: NR vs NR vs 25.9
AtTEnd^[45]	dMMR: NR vs 6.9 (HR: 0.36); Overall: 10.1 vs 8.9 (HR: 0.74)		NA			Overall: 38.7 vs 30.2 (HR: 0.82)
KEYNOTE-146^[46-48]	dMMR: 26.4; pMMR: 7.4; Overall: 7.4		NA			dMMR: NR; pMMR: 17.2; Overall: 17.7
KEYNOTE-775^[49-50]	pMMR: 6.6 vs 3.8 (HR: 0.60); Overall: 7.2 vs 3.8 (HR: 0.56)		NA			pMMR: 17.4 vs 12.0 (HR: 0.68);Overall: 18.3 vs 11.4 (HR: 0.62)
CAP 04^[51]	pMMR-MSS: 8.1; Overall: 6.2		NA			Overall: 21.0

Study	Drug	Phase	Sample size/n	Biomarker	Primary endpoint	Secondary endpoint
NRG-GY018(KEYNOTE-868)^[41]	Pembrolizumab plus paclitaxel/carboplatin	Phase Ⅲ	dMMR: 225; pMMR: 591	MMR	PFS in patients with dMMR and pMMR	Safety, OS, and health-related quality of life
ENGOT-en11/GOG-3053(KEYNOTE-B21)^[42]	Pembrolizumab plus paclitaxel/carboplatin	Phase Ⅲ	dMMR: 281; pMMR: 814	MMR	DFS, OS	DFS, AEs, PROs
ENGOT-EN-6-NSGO/GOG-3031/RUBY^[43]	Dostarlimab plus paclitaxel/carboplatin	Phase Ⅲ	dMMR/MSI-H: 118; pMMR-MSS: 376	MSI/MMR	PFS in dMMR/MSI-H patients, overall PFS, and OS	PFS, ORR. DOR, etc.
DUO-E^[44]	Durvalumab/olaparib plus paclitaxel/carboplatin	Phase Ⅲ	718	MMR, PD-L1, HRRm	PFS	OS, safety, etc.
AtTEnd^[45]	Atezolizumab plus carboplatin/paclitaxel	Phase Ⅲ	551	MMR, PD-L1	PFS in dMMR patients and overall PFS and OS	ORR, DoR, PFS2, safety, etc.
KEYNOTE-146^[46-48]	Pembrolizumab plus lenvatinib	Phase Ⅰb /Ⅱ	108	MMR/MSI	ORR	ORR, DOR, PFS, OS, safety, etc.
KEYNOTE-775^[49-50]	Pembrolizumab plus lenvatinib	Phase Ⅲ	dMMR: 130; pMMR: 697	MMR	PFS and OS in patients with dMMR/pMMR	ORR
CAP 04^[51]	Camrelizumab plus apatinib	Phase Ⅰ	36	MMR/MSI, PD-L1	ORR	DCR, TTR, DOR, TTF, PFS, OS, safety, etc.
Study	mPFS and HR		PFS and HR			mOS and HR
NRG-GY018(KEYNOTE-868)^[41]	dMMR: NR vs 7.6 (HR: 0.30); pMMR: 13.1 vs 8.7 (HR: 0.54)		(12 months) dMMR: 74 vs 38 (HR: 0.30); pMMR: 13.1 vs 8.7 (HR: 0.54)			NA
ENGOT-en11/GOG-3053(KEYNOTE-B21)^[42]	NA		NA			NA
ENGOT-EN-6-NSGO/GOG-3031/RUBY^[43]	NA		(24 months) dMMR: 61.4 vs 15.7 (HR: 0.28); pMMR: 28.4 vs 18.8 (HR: 0.76); Overall: 36.1 vs 18.1 (HR: 0.64)			NA
DUO-E^[44]	CP+D+D, CP+D, and CP ITT: 15.1 vs 10.2 vs 9.6; dMMR: 31.8 vs NR vs 7.0; pMMR: 15.0 vs 9.9 vs 9.7		NA			CP+D+D, CP+D, and CP ITT: NR vs NR vs 25.9
AtTEnd^[45]	dMMR: NR vs 6.9 (HR: 0.36); Overall: 10.1 vs 8.9 (HR: 0.74)		NA			Overall: 38.7 vs 30.2 (HR: 0.82)
KEYNOTE-146^[46-48]	dMMR: 26.4; pMMR: 7.4; Overall: 7.4		NA			dMMR: NR; pMMR: 17.2; Overall: 17.7
KEYNOTE-775^[49-50]	pMMR: 6.6 vs 3.8 (HR: 0.60); Overall: 7.2 vs 3.8 (HR: 0.56)		NA			pMMR: 17.4 vs 12.0 (HR: 0.68);Overall: 18.3 vs 11.4 (HR: 0.62)
CAP 04^[51]	pMMR-MSS: 8.1; Overall: 6.2		NA			Overall: 21.0