BACKGROUND: SOT201 and its murine surrogate mSOT201 are novel cis-acting immunocytokines consisting of a humanized/murinized/, Fc-silenced anti-programmed cell death protein 1 (PD-1) monoclonal antibody (mAb) fused to an attenuated human interleukin (IL)-15 and the IL-15Rα sushi+ domain. Murine mPD1-IL2v is a conjugate of a murinized, Fc silenced anti-PD-1 mAb bearing human IL-2 with abolished IL-2Rα binding. These immunocytokines spatiotemporally reinvigorate PD-1+ CD8+ tumor-infiltrating lymphocytes (TILs) via cis-activation and concomitantly activate the innate immunity via IL-2/15Rβγ signaling. METHODS: Human peripheral blood mononuclear cell and cell lines were used to evaluate cis/trans activity of SOT201. Anti-PD-1 mAb responsive (MC38, CT26) and resistant (B16F10, CT26 STK11 KO) mouse tumor models were used to determine the anticancer efficacy, and the underlying immune cell activity was analyzed via single-cell RNA sequencing and flow cytometry. The expansion of tumor antigen-specific CD8+ T cells by mSOT201 or mPD1-IL2v and memory CD8+ T-cell generation in vivo was determined by flow cytometry. RESULTS: SOT201 delivers attenuated IL-15 to PD-1+ T cells via cis-presentation, reinvigorates exhausted human T cells and induces higher interferon-γ production than pembrolizumab in vitro. mSOT201 administered as a single dose exhibits strong antitumor efficacy with several complete responses in all tested mouse tumor models. While mPD1-IL2v activates CD8+ T cells with a 50-fold higher potency than mSOT201 in vitro, mSOT201 more effectively reactivates effector exhausted CD8+ T cells (Tex), which demonstrate higher cytotoxicity, lower exhaustion and lower immune checkpoint transcriptional signatures in comparison to mPD1-IL2v in MC38 tumors in vivo. This can be correlated with a higher rate of complete responses in the MC38 tumor model following mSOT201 treatment when compared with mPD1-IL2v. mSOT201 increased the relative number of tumor antigen-specific CD8+ T cells, and unlike mPD1-IL2v stimulated greater expansion of adoptively transferred ovalbumin-primed CD8+ T cells simultaneously limiting the peripheral CD8+ T-cell sink, leading to the development of memory CD8+ T cells in vivo. CONCLUSIONS: SOT201 represents a promising therapeutic candidate that preferentially targets PD-1+ TILs, delivering balanced cytokine activity for reviving CD8+ Tex cells in tumors. SOT201 is currently being evaluated in the Phase I clinical study VICTORIA-01 (NCT06163391) in patients with advanced metastatic cancer.
- Klíčová slova
- Cytokine, Immune Checkpoint Inhibitor, Immunotherapy, T cell, Tumor microenvironment - TME,
- MeSH
- antigeny CD279 * antagonisté a inhibitory MeSH
- CD8-pozitivní T-lymfocyty imunologie MeSH
- inhibitory kontrolních bodů farmakologie MeSH
- interleukin-15 * genetika farmakologie MeSH
- lidé MeSH
- myši MeSH
- nádorové buněčné linie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- antigeny CD279 * MeSH
- inhibitory kontrolních bodů MeSH
- interleukin-15 * MeSH
- PDCD1 protein, human MeSH Prohlížeč
The KEYNOTE-564 trial showed that adjuvant immune checkpoint inhibitor (ICI) therapy with pembrolizumab, a PD-1 antibody, significantly improved disease-free survival (DFS) and overall (OS) survival in localised clear-cell renal cell carcinoma (RCC) with a high risk of relapse. The TiNivo and CONTACT-03 trials have reported results for subsequent therapy after progression on ICI therapy in the metastatic setting. The European Association of Urology (EAU) RCC guidelines panel reassessed the new trial results to update recommendations for adjuvant therapy and post-adjuvant therapy. Adjuvant pembrolizumab significantly improved OS (hazard ratio 0.62, 95% confidence interval 0.44-0.87; p = 0.005). Recent trials of subsequent ICI after recurrence on ICI in the metastatic setting do not support ICI monotherapy or combination therapy in patients with recurrence on or after adjuvant ICI therapy. There are no prospective trial results for treatment after adjuvant pembrolizumab failure. On the basis of the recent results, the EAU RCC guidelines panel has updated the recommendation for adjuvant therapy and now issues a strong recommendation for adjuvant pembrolizumab. ICI monotherapy or combination therapy is not recommended in patients with recurrence during or shortly after adjuvant pembrolizumab. PATIENT SUMMARY: Treatment with an immunotherapy drug called pembrolizumab after surgery in patients with intermediate-risk or high-risk kidney cancer delays the time to recurrence of cancer and prolongs survival. Therefore, pembrolizumab after surgery is strongly recommended for these patients. However, a significant proportion of patients have life-changing or serious side effects and these must be discussed.
- Klíčová slova
- Adjuvant therapy, Clear cell histology, High risk, Metastasectomy, Overall survival, Pembrolizumab, Renal cell carcinoma, Tyrosine kinase inhibitor,
- MeSH
- adjuvantní chemoterapie MeSH
- humanizované monoklonální protilátky MeSH
- inhibitory kontrolních bodů * terapeutické užití škodlivé účinky MeSH
- karcinom z renálních buněk * farmakoterapie MeSH
- lidé MeSH
- nádory ledvin * farmakoterapie patologie MeSH
- směrnice pro lékařskou praxi jako téma MeSH
- urologie normy MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- směrnice pro lékařskou praxi MeSH
- úvodníky MeSH
- Geografické názvy
- Evropa MeSH
- Názvy látek
- humanizované monoklonální protilátky MeSH
- inhibitory kontrolních bodů * MeSH
- pembrolizumab MeSH Prohlížeč
Gender- and sex-based disparities in response to immune-checkpoint inhibitors (ICI) has been reported in a variety of tumor types. Women have different anatomy with recurrent urinary tract infections, a different sex hormonal profile, and intrinsic differences in local and systemic immune systems and urobiome composition. Existing literature data in a pan-cancer context reveal contradictory results, and real-world evidence in urothelial carcinoma (UC) is lacking. This was a real-world, multicenter, international, observational study to determine the sex effects on the clinical outcomes in metastatic urothelial carcinoma (mUC) patients progressing or recurring after platinum-based therapy and treated with pembrolizumab as a part of routine clinical care. A total of 1039 patients, treated from January 1st, 2016 to December 31st, 2023 in 68 cancer centers were included. Our data showed that women with metastatic urothelial carcinoma treated with pembrolizumab had shorter OS than men, with a 13% advantage in the 5-year OS rate for male patients. A deeper understanding of these results may inform sex-stratification in future prospective clinical trials and help develop strategies to reduce the magnitude of the sex disparities observed in urothelial cancer outcomes.
- Klíčová slova
- Immunotherapy, NCT05290038, Pembrolizumab, Sex differences, Urothelial Cancer,
- MeSH
- humanizované monoklonální protilátky * terapeutické užití MeSH
- inhibitory kontrolních bodů terapeutické užití MeSH
- karcinom z přechodných buněk farmakoterapie mortalita patologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory močového měchýře farmakoterapie mortalita patologie MeSH
- protinádorové látky imunologicky aktivní terapeutické užití MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- sexuální faktory MeSH
- urologické nádory farmakoterapie mortalita patologie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- pozorovací studie MeSH
- Názvy látek
- humanizované monoklonální protilátky * MeSH
- inhibitory kontrolních bodů MeSH
- pembrolizumab MeSH Prohlížeč
- protinádorové látky imunologicky aktivní MeSH
The mechanisms governing the abscopal effects of local radiotherapy in cancer patients remain an open conundrum. Here, we show that off-target intestinal low-dose irradiation (ILDR) increases the clinical benefits of immune checkpoint inhibitors or chemotherapy in eight retrospective cohorts of cancer patients and in tumor-bearing mice. The abscopal effects of ILDR depend on dosimetry (≥1 and ≤3 Gy) and on the metabolic and immune host-microbiota interaction at baseline allowing CD8+ T cell activation without exhaustion. Various strains of Christensenella minuta selectively boost the anti-cancer efficacy of ILDR and PD-L1 blockade, allowing emigration of intestinal PD-L1-expressing dendritic cells to tumor-draining lymph nodes. An interventional phase 2 study provides the proof-of-concept that ILDR can circumvent resistance to first- or second-line immunotherapy in cancer patients. Prospective clinical trials are warranted to define optimal dosimetry and indications for ILDR to maximize its therapeutic potential.
- Klíčová slova
- Christensenella minuta, bile acids, cancer, dendritic cells, gut microbiota, metabolomics, radiotherapy, tumor immunosurveillance,
- MeSH
- antigeny CD274 * antagonisté a inhibitory metabolismus imunologie MeSH
- CD8-pozitivní T-lymfocyty imunologie MeSH
- imunoterapie metody MeSH
- inhibitory kontrolních bodů * farmakologie terapeutické užití MeSH
- lidé středního věku MeSH
- lidé MeSH
- metastázy nádorů MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- nádory imunologie radioterapie terapie MeSH
- retrospektivní studie MeSH
- senioři MeSH
- střeva patologie účinky záření MeSH
- střevní mikroflóra MeSH
- zvířata MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- myši MeSH
- senioři MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- antigeny CD274 * MeSH
- CD274 protein, human MeSH Prohlížeč
- inhibitory kontrolních bodů * MeSH
In less than a decade, immune checkpoint inhibitors (ICIs) have transformed the management of mismatch repair-deficient (dMMR) and microsatellite instability-high (MSI) cancers. However, beyond colorectal cancer (CRC), much of the evidence is mostly derived from non-randomized phase II studies or post-hoc analyses of broader clinical trials. dMMR/MSI tumours represent a specific subgroup of gastro-esophageal adenocarcinomas (GEA), accounting for approximately 9 % of cases, with a higher prevalence in early-stage compared to advanced-stage disease and older female patients. These tumours are predominantly sporadic, often linked to MLH1 promoter methylation, and rarely exhibit HER2 overexpression/ERBB2 amplification or other oncogenic drivers. The treatment landscape for early stage dMMR/MSI GEA is likely to change substantially soon, as ICIs have shown high pathological complete response (pCR) rates in small phase II trials, raising questions on optimisation of neoadjuvant therapy, and paving the way for organ preservation. The standard of treatment for untreated patients with advanced dMMR/MSI GEA is chemotherapy + ICI irrespectively of PDL-1 status. However, the role of chemotherapy-free regimen consisting of CTLA-4 plus PD-1 inhibitors remains undetermined. This review addresses these and other emerging questions, offering expert opinions and insights into the future therapeutic landscape for dMMR/MSI GEA.
- Klíčová slova
- Esophageal cancer, Gastric cancer, Immune checkpoint inhibitors, MSI, dMMR/MSI gastro-esophageal adenocarcinoma,
- MeSH
- adenokarcinom * farmakoterapie genetika patologie terapie MeSH
- inhibitory kontrolních bodů terapeutické užití MeSH
- lidé MeSH
- mikrosatelitní nestabilita * MeSH
- nádory jícnu * farmakoterapie genetika patologie MeSH
- nádory žaludku * farmakoterapie genetika patologie terapie MeSH
- oprava chybného párování bází DNA * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- inhibitory kontrolních bodů MeSH
Nanrilkefusp alfa (nanril; SOT101) is an interleukin (IL)-15 receptor βγ superagonist that stimulates natural killer (NK) and CD8+ T cells, thereby promoting an innate and adaptive anti-tumor inflammatory microenvironment in mouse tumor models either in monotherapy or combined with an anti-programmed cell death protein 1 (PD-1) antibody. In cynomolgus monkeys, a clinical schedule was identified, which translated into the design of a phase 1/1b clinical trial, AURELIO-03 (NCT04234113). In 51 patients with advanced/metastatic solid tumors, nanril increased the proportions of CD8+ T cells and NK cells in peripheral blood and tumors. It had a favorable safety profile when administered subcutaneously on days 1, 2, 8, and 9 of each 21-day cycle as monotherapy (0.25-15 μg/kg) or combined (1.5-12 μg/kg) with the anti-PD-1 pembrolizumab (200 mg). The most frequent treatment-emergent adverse events were pyrexia, injection site reactions, and chills. Furthermore, early clinical efficacy was observed, including in immune checkpoint blockade-resistant/refractory patients.
- Klíčová slova
- SOT101, anti-tumor efficacy, nanril, nanrilkefusp alfa, pembrolizumab combination, solid tumors,
- MeSH
- antigeny CD279 * antagonisté a inhibitory imunologie MeSH
- buňky NK imunologie účinky léků MeSH
- CD8-pozitivní T-lymfocyty imunologie účinky léků MeSH
- dospělí MeSH
- humanizované monoklonální protilátky terapeutické užití farmakologie MeSH
- inhibitory kontrolních bodů farmakologie terapeutické užití MeSH
- lidé středního věku MeSH
- lidé MeSH
- Macaca fascicularis MeSH
- nádory * farmakoterapie patologie imunologie MeSH
- senioři MeSH
- zvířata MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze I MeSH
- Názvy látek
- antigeny CD279 * MeSH
- humanizované monoklonální protilátky MeSH
- inhibitory kontrolních bodů MeSH
Advances in cancer treatments have significantly improved their effectiveness, yet access to first-line therapies remains limited. A 2017 survey revealed that over 25 % of metastatic melanoma patients in Europe lacked access to recommended therapies. To address this, the European Association of Dermato-Oncology and the European Melanoma Registry conducted a follow-up study on the registration and reimbursement of first-line treatments.A web-based survey using LimeSurvey was distributed to melanoma experts across 27 European countries from February to April 2022 and updated from February to April 2024. The questionnaire covered the percentage of patients receiving recommended treatments, as well as treatment authorization and reimbursement dates for systemic and adjuvant therapies.There has been significant improvement in the registration and reimbursement of BRAFi/MEKi, anti-PD1, and anti-PD1/anti-CTLA4 therapies, increasing from 48 %, 63 %, and 37 % in 2017 to 96 %, 96 %, and 78 % in 2024, respectively. Despite these gains, restrictions persist. Anti-PD1/anti-CTLA4 combination immunotherapy is still not available without restrictions in 48 % of the surveyed countries. The nivolumab/relatlimab combination is licensed only for PDL-1-negative melanoma and reimbursed in seven countries of Europe. Tebentafusp is reimbursed in 15 countries and talimogene laherpervec in 5. In 2024, adjuvant treatments for stage III melanoma are reimbursed in 22 countries for dabrafenib/trametinib and 24 of 27 for anti-PD1 antibodies. Pembrolizumab and nivolumab are reimbursed in 15 and 8 countries, respectively, for stage IIB/IIC disease.While there have been improvements in the reimbursement of metastatic melanoma treatments in Europe, challenges and discrepancies remain. Further efforts at European and global levels are needed to harmonize and enhance access to cancer medicines.
- Klíčová slova
- Access to medicines, Cancer care, Disparities, Immunotherapy, Melanoma, Targeted therapy,
- MeSH
- dostupnost zdravotnických služeb MeSH
- imunoterapie metody MeSH
- inhibitory kontrolních bodů terapeutické užití MeSH
- lidé MeSH
- melanom * farmakoterapie MeSH
- nádory kůže * farmakoterapie MeSH
- průzkumy a dotazníky MeSH
- registrace * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Evropa MeSH
- Názvy látek
- inhibitory kontrolních bodů MeSH
BACKGROUND: Recently, a plethora of novel systemic agents have been incorporated into the therapeutic armamentarium of advanced urothelial carcinoma (aUC). The antibody-drug conjugate (ADC), enfortumab vedotin (EV), has demonstrated relevant clinical benefit in patients with aUC refractory to platinum and immune-checkpoint inhibitor (ICI) therapy. Our study provides a retrospective, international, real-world analysis comparing the effectiveness of EV to chemotherapy in this setting. METHODS: The data were extracted from the medical records of patients treated with EV or chemotherapy following pembrolizumab for recurrent or progressive aUC after platinum-based chemotherapy. Patients were assessed for overall survival (OS), progression-free survival (PFS), overall response rate (ORR) and duration of response (DoR). RESULTS: Our analysis included 247 patients treated with EV (88, 36%) or chemotherapy (159, 64%). Median OS was 9.1 months (95%CI 7.2-10.7) in the overall study population, 13.6 months (95%CI 10.0-31.0) in patients receiving EV and 6.8 months (95%CI 6.0-8.9) in patients receiving chemotherapy (p < 0.001). The OS benefit of EV was not affected by primary tumour site and histology, metastatic sites, type of first platinum-based chemotherapy or response to pembrolizumab. In the EV cohort, the median PFS was significantly longer (8.8 months [95%CI 6.5-17.0] vs. 3.0 months [95%CI 2.6-3.7]) and the ORR was significantly higher (56% vs. 23%) than in the chemotherapy cohort. CONCLUSIONS: The results of our international analysis of real-world data confirm the effectiveness of EV in the sequential strategy of aUC patients who have received prior platinum-based chemotherapy and anti-PD-1 pembrolizumab, regardless of commonly considered prognostic factors. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT05290038.
- Klíčová slova
- ARON‐2 study, NCT05290038, chemotherapy, enfortumab vedotin, pembrolizumab, real‐world data, sequencing, urothelial carcinoma,
- MeSH
- doba přežití bez progrese choroby MeSH
- dospělí MeSH
- humanizované monoklonální protilátky * terapeutické užití aplikace a dávkování MeSH
- inhibitory kontrolních bodů terapeutické užití MeSH
- karcinom z přechodných buněk farmakoterapie mortalita patologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- monoklonální protilátky terapeutické užití aplikace a dávkování MeSH
- protokoly protinádorové kombinované chemoterapie * terapeutické užití MeSH
- retrospektivní studie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- urologické nádory farmakoterapie patologie mortalita MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- Názvy látek
- enfortumab vedotin MeSH Prohlížeč
- humanizované monoklonální protilátky * MeSH
- inhibitory kontrolních bodů MeSH
- monoklonální protilátky MeSH
- pembrolizumab MeSH Prohlížeč
Recent phase 3 randomized controlled trials (RCTs) demonstrate the promising impact of immune checkpoint inhibitor (ICI)-based combination therapies on locally advanced or metastatic urothelial carcinoma (UC). However, comparative data on the efficacy and toxicity of different ICI-based combinations are lacking. This study aims to compare the efficacy of first-line ICI-based combination therapies for locally advanced or metastatic UC using phase 3 RCT data. In November 2023, three databases were searched for RCTs evaluating oncological outcomes in patients with locally advanced or metastatic UC who were treated with first-line ICI-based combination therapies. Network meta-analysis (NMA) was conducted to compare outcomes, including overall survival (OS), progression-free survival (PFS), objective response rates (ORRs), complete response rates (CRRs), and treatment-related adverse events (TRAEs). Subgroup analyses were based on PD-L1 status and cisplatin eligibility. The NMA included five RCTs. Enfortumab vedotin (EV) + pembrolizumab ranked the highest for improving OS (100%), PFS (100%), ORR (96%), and CRR (96%), followed by nivolumab + chemotherapy. EV + pembrolizumab combination superiority held across PD-L1 status and cisplatin eligibility. In patients who are cisplatin-eligible, EV + pembrolizumab significantly improved OS (HR: 0.68, 95%CI 0.47-0.99) and PFS (HR: 0.67, 95%CI 0.49-0.92) compared to nivolumab + chemotherapy. Durvalumab + tremelimumab was the safest combination for severe TRAEs, and EV + pembrolizumab ranked second. Our analyses support EV + pembrolizumab combination as a first-line treatment for locally advanced or metastatic UC. Thus, EV + pembrolizumab may become a guideline-changing standard treatment.
- Klíčová slova
- Chemotherapy, Enfortumab vedotin, Immune checkpoint inhibitors, Metastasis, Urothelial carcinoma,
- MeSH
- humanizované monoklonální protilátky terapeutické užití aplikace a dávkování škodlivé účinky MeSH
- inhibitory kontrolních bodů * terapeutické užití MeSH
- karcinom z přechodných buněk farmakoterapie mortalita patologie MeSH
- lidé MeSH
- metastázy nádorů MeSH
- monoklonální protilátky MeSH
- nádory močového měchýře farmakoterapie patologie mortalita MeSH
- protokoly protinádorové kombinované chemoterapie * terapeutické užití škodlivé účinky MeSH
- randomizované kontrolované studie jako téma MeSH
- urologické nádory farmakoterapie mortalita patologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- síťová metaanalýza MeSH
- systematický přehled MeSH
- Názvy látek
- enfortumab vedotin MeSH Prohlížeč
- humanizované monoklonální protilátky MeSH
- inhibitory kontrolních bodů * MeSH
- monoklonální protilátky MeSH
- pembrolizumab MeSH Prohlížeč
PURPOSE: Patients with high-grade serous ovarian carcinoma (HGSOC) are virtually insensitive to immune checkpoint inhibitors (ICI) employed as standalone therapeutics, at least in part reflecting microenvironmental immunosuppression. Thus, conventional chemotherapeutics and targeted anticancer agents that not only mediate cytotoxic effects but also promote the recruitment of immune effector cells to the HGSOC microenvironment stand out as promising combinatorial partners for ICIs in this oncological indication. EXPERIMENTAL DESIGN: We harnessed a variety of transcriptomic, spatial, and functional assays to characterize the differential impact of neoadjuvant paclitaxel-carboplatin on the immunological configuration of paired primary and metastatic HGSOC biopsies as compared to neoadjuvant chemotherapy (NACT)-naïve HGSOC samples from five independent patient cohorts. RESULTS: We found NACT-driven endoplasmic reticulum stress and calreticulin exposure in metastatic HGSOC lesions culminates with the establishment of a dense immune infiltrate including follicular T cells (TFH cells), a prerequisite for mature tertiary lymphoid structure (TLS) formation. In this context, TLS maturation was associated with an increased intratumoral density of ICI-sensitive TCF1+PD1+ CD8+ T cells over their ICI-insensitive TIM-3+PD1+ counterparts. Consistent with this notion, chemotherapy coupled with a PD1-targeting ICI provided a significant survival benefit over either therapeutic approach in syngeneic models of HGSOC bearing high (but not low) tumor mutational burden. CONCLUSIONS: Altogether, our findings suggest that NACT promotes TLS formation and maturation in HGSOC lesions, de facto preserving an intratumoral ICI-sensitive T-cell phenotype. These observations emphasize the role of rational design, especially relative to the administration schedule, for clinical trials testing chemotherapy plus ICIs in patients with HGSOC. See related commentary by Bravo Melgar and Laoui, p. 10.
- MeSH
- CD8-pozitivní T-lymfocyty * imunologie účinky léků MeSH
- ektopické lymfoidní struktury * imunologie patologie MeSH
- hepatocytární jaderný faktor 1-alfa * genetika metabolismus MeSH
- inhibitory kontrolních bodů * terapeutické užití farmakologie MeSH
- karboplatina aplikace a dávkování farmakologie terapeutické užití MeSH
- lidé MeSH
- nádorové mikroprostředí * imunologie účinky léků MeSH
- nádory vaječníků * farmakoterapie imunologie patologie MeSH
- neoadjuvantní terapie metody MeSH
- paclitaxel aplikace a dávkování terapeutické užití farmakologie MeSH
- protokoly protinádorové kombinované chemoterapie terapeutické užití farmakologie MeSH
- serózní cystadenokarcinom farmakoterapie patologie imunologie MeSH
- stres endoplazmatického retikula účinky léků imunologie MeSH
- tumor infiltrující lymfocyty imunologie účinky léků metabolismus MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- hepatocytární jaderný faktor 1-alfa * MeSH
- inhibitory kontrolních bodů * MeSH
- karboplatina MeSH
- paclitaxel MeSH