ReviewMechanismMixed resultsLimited evidenceTier 4 · clinical
International journal of gynecological cancer : official journal of the International Gynecological Cancer Society · Jan 2026
uterine leiomyosarcoma
This is a narrative review of the immune environment of uterine leiomyosarcoma and the potential role of immune checkpoint inhibitors. The authors report variable PD-L1 expression, heterogeneous lymphocytic infiltration, and interactions with tumor-associated macrophages, note modest response rates to checkpoint inhibitors in clinical trials, and discuss that dual PD-1/CTLA-4 blockade and chemotherapy-induced immunogenic cell death may enhance immune activation in select patients. They conclude that combinatorial and personalized strategies, improved immune profiling, and macrophage-targeted approaches merit further study.
Studied with: anti-CTLA-4 + anti-PD-1 dual checkpoint blockade, chemotherapy (to induce immunogenic cell death), targeted immunomodulation, macrophage-targeted therapies.
Key findings
- Uterine leiomyosarcoma has a variable tumor immune microenvironment including variable PD-L1 expression and differential lymphocytic infiltration.
- Interactions with tumor-associated macrophages shape immune responses in leiomyosarcoma.
- Clinical trials of immune checkpoint inhibitors in leiomyosarcoma have produced modest response rates.
- Molecular analyses suggest that specific sub-groups of leiomyosarcoma patients may derive greater benefit from checkpoint inhibition.
- Dual-checkpoint blockade combining anti-PD-1 and anti-CTLA-4 has demonstrated enhanced immune activation in select patients.
- Chemotherapy-induced immunogenic cell death has been explored as a complementary approach to immunotherapy.
- Authors recommend innovative combinatorial strategies, improved patient selection, enhanced macrophage-targeted therapies, and optimized immune profiling for future research.
Limitations: Narrative review only—no new primary experimental or patient-level data are presented.; Conclusions are based on heterogeneous published studies and molecular analyses rather than definitive randomized trial evidence.; Abstract reports only 'modest response rates' in trials without quantitative pooled estimates or meta-analysis.; Leiomyosarcoma heterogeneity and rarity limit generalizability of existing trial results (as noted by authors)..
AI summary of the abstract, human-reviewed · Jun 2026. Describes what this study reported, not medical advice. View on PubMed
Human · observationalReported positiveLimited evidenceTier 3 · early humann = 10
BMC cancer · Dec 2024 · retrospective cohort
Trastuzumab-deruxtecan-t-dxdTrastuzumab-deruxtecanendometrial neoplasmsovarian neoplasmscervical neoplasmsuterine carcinosarcomauterine leiomyosarcomauterine serous carcinomaovarian carcinosarcomahigh-grade serous ovarian carcinomamucinous ovarian carcinomasquamous cervical carcinoma This retrospective single-center study identified 10 patients with HER2-expressing (IHC 2+/3+) recurrent or metastatic gynecological cancers who received trastuzumab deruxtecan (5.4 mg/kg IV every 3 weeks). The cohort had a median progression-free survival of 5.4 months (95% CI 0.8-9.8). Five patients had a partial response, one had stable disease at 12 weeks, and four had disease progression at initial assessment. Clinical benefit was observed mainly in tumors with HER2 IHC 3+.
Reported effects: median PFS 5.4 mo [0.8–9.8], n=10 · partial responses 5, n=10 · +2 more
Key findings
- 10 patients with recurrent/metastatic HER2-expressing gynecological malignancies were treated with T-DXd.
- Histologies included uterine neoplasms (n=5), cervical squamous carcinoma (n=1) and ovarian cancers (n=4).
- Median age was 65.4 years (25th-75th percentile, 58.1-75.2 years).
- HER2 by IHC: 5 patients were 3+ and 5 patients were 2+.
- Median number of prior therapy lines was 4 (range 2-6); 2 uterine serous carcinoma patients were pretreated with trastuzumab and 4 patients had prior immunotherapy.
- Dose: T-DXd 5.4 mg/kg IV every 3 weeks until progression/toxicity.
- Median progression-free survival (PFS) in the cohort was 5.4 months (95% CI 0.8-9.8 months).
- Responses: 5 patients had partial response (including 2 previously treated with trastuzumab), 1 patient had stable disease at 12 weeks, 4 patients had disease progression at initial assessment.
- Most patients who derived clinical benefit had HER2 IHC 3+ expression.
Limitations: Retrospective, single-center design; Very small sample size (n=10); No control or comparator arm; Heterogeneous mix of gynecologic histologies; Heavily pre-treated population limits generalizability; Limited/absent reporting of safety or adverse event data in the abstract; Potential selection and reporting bias inherent to retrospective series.
AI summary of the abstract, human-reviewed · Jun 2026. Describes what this study reported, not medical advice. View on PubMed · Full text
ReviewMechanismInconclusiveLimited evidenceTier 4 · clinical
Yi chuan = Hereditas · Aug 2024 · review
uterine leiomyosarcoma
This article is a review of the molecular pathology of uterine leiomyosarcoma (uLMS). The authors summarize molecular genetic features, epigenetic variants, experimental models, and clinical research progress, and note that understanding of uLMS pathogenesis is inadequate and disease models are limited, which hinders development of effective therapies.
Key findings
- uLMS is an aggressive malignant soft-tissue tumor arising from the myometrium that is difficult to distinguish from benign leiomyoma in early stages and has a poor prognosis.
- Current studies of uLMS pathogenesis and disease biology are inadequate.
- uLMS disease models are very limited, which hinders development of effective therapeutics.
- The review systematically summarizes molecular genetic features, epigenetic alterations, experimental models, and clinical research progress, and discusses directions including tumor evolution, the tumor microenvironment, and therapy development.
Limitations: This publication is a review and does not present new primary experimental or clinical data.; Abstract does not describe review methods in detail (e.g., search strategy, inclusion criteria).; Field-level limitations noted by the authors include inadequate pathogenesis studies and limited disease models, which constrain conclusions about therapeutic development..
AI summary of the abstract, human-reviewed · Jun 2026. Describes what this study reported, not medical advice. View on PubMed