BACKGROUND: The programmed cell death ligand-1 (PD-L1)/programmed cell death-1 (PD-1) pathway is important in metastatic renal cell carcinoma (mRCC). However, some dissimilarities between anti-PD-1 and anti-PD-L1 inhibitors have emerged. We aimed to assess differences between anti-PD-1 and anti-PD-L1 combination immunotherapies as first-line treatments in mRCC patients. METHODS: Multiple databases (PubMed, Web of Science, and Scopus) were searched for articles published until March 2021. Studies were eligible if they compared overall survival (OS), progression-free survival (PFS), objective response rates (ORR), complete response rates (CRR), and adverse events. RESULTS: Five studies met the eligibility criteria. PD-1 combination therapy was associated with significantly better OS and PFS and higher ORR and CRR than sunitinib (hazard ratio [HR]: 0.60, 95% confidence interval [CI]: 0.40-0.89; HR: 0.52, 95% CI: 0.37-0.75; odds ratio [OR]: 3.20, 95% CI: 2.18-4.68; and OR: 3.05, 95% CI: 2.13-4.37, respectively; P < 0.001). For all oncological outcomes, anti-PD-1 agents were superior to anti-PD-L1 agents based on HR and OR (OS: HR = 0.88, PFS: HR = 0.76, ORR: OR = 1.85, and CRR: OR = 2.24). Conversely, anti-PD-L1 agents were superior to anti-PD-1 agents in their safety profiles. In network meta-analyses, pembrolizumab plus lenvatinib seemed the worst tolerated anti-PD-1 combination therapy. CONCLUSIONS: Our analysis indicates the superior oncologic benefits of first-line anti-PD-1 combination therapies over anti-PD-L1 combination therapies in mRCC patients. This biological difference is of vital importance for clinical treatment decision making and the design of future rational combination therapy trials in mRCC.

• Klíčová slova
• Combination therapy, Meta-analysis, Metastatic renal cell carcinoma, Programmed cell death-1 inhibitors, Programmed cell death-ligand 1 inhibitors,
• MeSH
• antigeny CD274 antagonisté a inhibitory   imunologie   MeSH
• antigeny CD279 antagonisté a inhibitory   imunologie   MeSH
• inhibitory kontrolních bodů aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• karcinom z renálních buněk farmakoterapie   imunologie   MeSH
• klinické zkoušky, fáze III jako téma MeSH
• lidé MeSH
• nádory ledvin farmakoterapie   imunologie   MeSH
• protokoly protinádorové kombinované chemoterapie škodlivé účinky   terapeutické užití   MeSH
• randomizované kontrolované studie jako téma MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• systematický přehled MeSH
• Názvy látek
• antigeny CD274 MeSH
• antigeny CD279 MeSH
• CD274 protein, human MeSH Prohlížeč
• inhibitory kontrolních bodů MeSH
• PDCD1 protein, human MeSH Prohlížeč

Fumarate hydratase-deficient renal cell carcinoma (FH-RCC) is a rare and aggressive tumor affecting mostly younger patients. This is the first study to assess the expression of programmed death-1 (PD-1) receptor/PD-1 ligand (PD-L1) in FH-RCC. Formalin-fixed paraffin-embedded samples from 13 FH-RCCs collected in an international multi-institutional study, were evaluated by immunohistochemistry (IHC) for PD-1/PD-L1 reactivity in tumor cells and tumor infiltrating lymphocytes (TILs). PD-1/PD-L1 expression was further evaluated by qPCR. By IHC, PD-1 was negative in tumor cells in all 13 cases. PD-L1 was positive in tumor cells in 2/13 cases, weak positive in 7/13, and negative in 4/13 cases, respectively. In TILs, PD-1 was positive in 1/13, weak positive in 3/13, and negative in 9/13 cases. In TILs, PD-L1 was weak positive by IHC in 5/13, and negative in 8/13 cases, respectively. qPCR confirmed the result for 2 of 3 IHC weak positive PD-1 samples. Of 7 IHC weak positive samples (in tumor cells), PD-L1 mRNA was detected in all 7 tumors. The majority of FH-RCCs did not express PD-1/PD-L1 by IHC, which was confirmed by molecular analysis. PD-1/PD-L1 expression in FH-RCC is restricted to a proportion of cases which may benefit from targeted therapies.

• Klíčová slova
• Fumarate hydratase-deficient renal cell carcinoma, Kidney, PD-1 ligand (PD-L1) receptor, Programmed death-1 (PD-1) receptor,
• MeSH
• antigeny CD274 metabolismus   MeSH
• antigeny CD279 metabolismus   MeSH
• dospělí MeSH
• fumarasa nedostatek   metabolismus   MeSH
• imunohistochemie metody   MeSH
• karcinom z renálních buněk metabolismus   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory ledvin metabolismus   patologie   MeSH
• přežití bez známek nemoci MeSH
• tumor infiltrující lymfocyty metabolismus   patologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antigeny CD274 MeSH
• antigeny CD279 MeSH
• CD274 protein, human MeSH Prohlížeč
• fumarasa MeSH
• PDCD1 protein, human MeSH Prohlížeč

BACKGROUND: Immune checkpoint inhibitors (ICI) targeting the programmed cell death protein 1 (PD-1) signaling pathway have dramatically improved the clinical outcomes of oncological patients having advanced non-small cell lung carcinoma (NSCLC). The immunohistochemical analysis of programmed death-ligand 1 (PD-L1) expression remains the most widely used and clinically validated bio-marker predicting efficacy of ICI in NSCLC patients, but it represents in isolation an imperfect tool. The PD-1 axis is intricately coupled with numerous cellular and molecular factors within the tumor microenvironment (TME) of NSCLC. Cellular factors implicated in the regulation process of PD-L1 expression in NSCLC are related to the activity of tumor infiltrating lymphocytes and cancer associated fibroblasts. Intrinsic molecular factors which affect the level of PD-L1 expression are associated with the presence of oncogenic driver mutations in the Kirsten rat sarcoma viral oncogene homolog and epidermal growth factor receptor genes and to rearrangements in the anaplastic lymphoma kinase. Furthermore, activation of hypoxic signaling pathways and the transforming growth factor beta 1 axis can have an impact on the level of PD-L1 expression in NSCLC. A deeper understanding of the complex mechanisms regulating PD-L1 expression is necessary to tailor the treatment with ICI in patients with advanced NSCLC. PURPOSE: In this review, we present an overview of key factors underlying the regulation of PD-L1 expression within the TME of NSCLC, which are, and potentially can be, exploited to improve the outcomes of immunotherapy targeting the PD-1 axis.

• Klíčová slova
• epithelial to mesenchymal transition, hypoxia -inducible factor-1α, immune checkpoint inhibitors, non-small cell lung carcinoma, programmed cell death protein 1, programmed death-ligand 1, tumor infiltrating lymphocytes, tumour infiltrating lymphocytes,
• MeSH
• antigeny CD274 * genetika   metabolismus   MeSH
• antigeny CD279 * genetika   metabolismus   MeSH
• biologické markery MeSH
• lidé MeSH
• nádorové mikroprostředí genetika   MeSH
• nádory plic * farmakoterapie   genetika   MeSH
• nemalobuněčný karcinom plic * farmakoterapie   genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• antigeny CD274 * MeSH
• antigeny CD279 * MeSH
• biologické markery MeSH
• CD274 protein, human MeSH Prohlížeč

The PD-1/PD-L1 complex is an immune checkpoint responsible for regulating the natural immune response, but also allows tumors to escape immune surveillance. Inhibition of the PD-1/PD-L1 axis positively contributes to the efficacy of cancer treatment. The only available therapeutics targeting PD-1/PD-L1 are monoclonal antibody-based drugs, which have several limitations. Therefore, small molecule compounds are emerging as an attractive alternative that can potentially overcome the drawbacks of mAb-based therapy. In this article, we present a novel class of small molecule compounds based on the terphenyl scaffold that bind to PD-L1. The general architecture of the presented structures is characterized by axial symmetry and consists of three elements: an m-terphenyl core, an additional aromatic ring, and a solubilizing agent. Using molecular docking, we designed a series of final compounds, which were subsequently synthesized and tested in HTRF assay and NMR binding assay to evaluate their activity. In addition, we performed an in-depth analysis of the mutual arrangement of the phenyl rings of the terphenyl core within the binding pocket of PD-L1 and found several correlations between the plane angle values and the affinity of the compounds towards the protein.

• Klíčová slova
• C2-symmetrical ligands, PD-L1, cancer, immune checkpoint, small molecule inhibitor,
• MeSH
• antigeny CD274 * antagonisté a inhibitory   metabolismus   chemie   MeSH
• antigeny CD279 * antagonisté a inhibitory   metabolismus   chemie   MeSH
• inhibitory kontrolních bodů chemie   farmakologie   MeSH
• knihovny malých molekul farmakologie   chemie   MeSH
• lidé MeSH
• molekulární struktura MeSH
• simulace molekulového dockingu * MeSH
• terfenylové sloučeniny * chemie   farmakologie   MeSH
• vazba proteinů * MeSH
• vazebná místa MeSH
• vztahy mezi strukturou a aktivitou MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antigeny CD274 * MeSH
• antigeny CD279 * MeSH
• CD274 protein, human MeSH Prohlížeč
• inhibitory kontrolních bodů MeSH
• knihovny malých molekul MeSH
• PDCD1 protein, human MeSH Prohlížeč
• terfenylové sloučeniny * MeSH

Purpose Hodgkin Reed-Sternberg (HRS) cells evade antitumor immunity by multiple means, including gains of 9p24.1/ CD274(PD-L1)/ PDCD1LG2(PD-L2) and perturbed antigen presentation. Programmed death 1 (PD-1) receptor blockade is active in classic Hodgkin lymphoma (cHL) despite reported deficiencies of major histocompatibility complex (MHC) class I expression on HRS cells. Herein, we assess bases of sensitivity to PD-1 blockade in patients with relapsed/refractory cHL who were treated with nivolumab (anti-PD-1) in the CheckMate 205 trial. Methods HRS cells from archival tumor biopsies were evaluated for 9p24.1 alterations by fluorescence in situ hybridization and for expression of PD ligand 1 (PD-L1) and the antigen presentation pathway components-β2-microglobulin, MHC class I, and MHC class II-by immunohistochemistry. These parameters were correlated with clinical responses and progression-free survival (PFS) after PD-1 blockade. Results Patients with higher-level 9p24.1 copy gain and increased PD-L1 expression on HRS cells had superior PFS. HRS cell expression of β2-microglobulin/MHC class I was not predictive for complete remission or PFS after nivolumab therapy. In contrast, HRS cell expression of MHC class II was predictive for complete remission. In patients with a > 12-month interval between myeloablative autologous stem-cell transplantation and nivolumab therapy, HRS cell expression of MHC class II was associated with prolonged PFS. Conclusion Genetically driven PD-L1 expression and MHC class II positivity on HRS cells are potential predictors of favorable outcome after PD-1 blockade. In cHL, clinical responses to nivolumab were not dependent on HRS cell expression of MHC class I.

• MeSH
• antigeny CD274 antagonisté a inhibitory   biosyntéza   genetika   imunologie   MeSH
• antigeny CD279 antagonisté a inhibitory   biosyntéza   genetika   imunologie   MeSH
• beta-2-mikroglobulin biosyntéza   genetika   imunologie   MeSH
• buňky Reedové-Sternberga účinky léků   imunologie   patologie   MeSH
• doba přežití bez progrese choroby MeSH
• Hodgkinova nemoc farmakoterapie   genetika   imunologie   patologie   MeSH
• kohortové studie MeSH
• lidé MeSH
• lidské chromozomy, pár 9 MeSH
• MHC antigeny II. třídy biosyntéza   genetika   imunologie   MeSH
• nivolumab terapeutické užití   MeSH
• prediktivní hodnota testů MeSH
• prezentace antigenu MeSH
• protinádorové látky imunologicky aktivní terapeutické užití   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze II MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• antigeny CD274 MeSH
• antigeny CD279 MeSH
• B2M protein, human MeSH Prohlížeč
• beta-2-mikroglobulin MeSH
• CD274 protein, human MeSH Prohlížeč
• MHC antigeny II. třídy MeSH
• nivolumab MeSH
• PDCD1 protein, human MeSH Prohlížeč
• protinádorové látky imunologicky aktivní MeSH

CONTEXT: Immune-checkpoint inhibitors (ICIs) are a mainstay treatment of metastatic renal cell carcinoma (mRCC). As not all patients benefit from ICIs, a biomarker-driven clinical decision-making strategy is desirable. OBJECTIVE: To assess the predictive value of programmed death ligand 1 (PD-L1) in mRCC patients treated with ICIs. EVIDENCE ACQUISITION: Multiple databases were searched for articles published up to April 2020 according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement. Studies comparing objective response rate (ORR), complete response rate (CRR), progressive disease rate (PDR), or progression-free survival (PFS) based on tumor PD-L1 status in mRCC patients were eligible. EVIDENCE SYNTHESIS: Six studies matched our eligibility criteria. Treatment with ICIs was associated with significantly higher ORRs and CRRs, and lower PDRs in patients with PD-L1-positive tumors than in those with PD-L1-negative status (odds ratio [OR] 1.84, 95% confidence interval [CI] 1.48-2.28; OR 3.11, 95% CI 2.04-4.75; and OR 0.43, 95% CI 0.31-0.60, respectively). ICI treatment was associated with significantly better PFS in PD-L1-positive patients than in sunitinib-treated patients (hazard ratio 0.65, 95% CI 0.57-0.74), whereas this was not found in patients with PD-L1-negative tumors. Compared with sunitinib, ICI combination therapy improved ORRs and PFS significantly in PD-L1-positive patients of all examined ICIs. Nivolumab plus ipilimumab had the highest likelihood of providing the highest ORR and longest PFS in PD-L1-positive patients. CONCLUSIONS: PD-L1 positivity of the tumor is associated with improved ORRs and prolonged PFS in mRCC patients receiving ICI treatment and thus helps identify mRCC patients most likely to benefit from ICI treatment. PATIENT SUMMARY: The use of an immune-checkpoint inhibitor for the treatment of metastatic renal cell carcinoma (mRCC) improved oncological outcomes, and the status of programmed death ligand 1 could contribute to guiding patients and clinicians when determining personalized treatment strategies for mRCC.

• Klíčová slova
• Immune-checkpoint inhibitor, Meta-analysis, Programmed death ligand 1, Renal cell carcinoma,
• MeSH
• antigeny CD274 MeSH
• inhibitory kontrolních bodů MeSH
• karcinom z renálních buněk * farmakoterapie   MeSH
• lidé MeSH
• nádory ledvin * farmakoterapie   MeSH
• sunitinib terapeutické užití   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• systematický přehled MeSH
• Názvy látek
• antigeny CD274 MeSH
• inhibitory kontrolních bodů MeSH
• sunitinib MeSH

Several therapeutic monoclonal antibodies approved by the FDA are available against the PD-1/PD-L1 (programmed death 1/programmed death ligand 1) immune checkpoint axis, which has been an unprecedented success in cancer treatment. However, existing therapeutics against PD-L1, including small molecule inhibitors, have certain drawbacks such as high cost and drug resistance that challenge the currently available anti-PD-L1 therapy. Therefore, this study presents the screening of 32,552 compounds from the Natural Product Atlas database against PD-L1, including three steps of structure-based virtual screening followed by binding free energy to refine the ideal conformation of potent PD-L1 inhibitors. Subsequently, five natural compounds, i.e., Neoenactin B1, Actinofuranone I, Cosmosporin, Ganocapenoid A, and 3-[3-hydroxy-4-(3-methylbut-2-enyl)phenyl]-5-(4-hydroxybenzyl)-4-methyldihydrofuran-2(3H)-one, were collected based on the ADMET (absorption, distribution, metabolism, excretion, and toxicity) profiling and binding free energy (>−60 kcal/mol) for further computational investigation in comparison to co-crystallized ligand, i.e., JQT inhibitor. Based on interaction mapping, explicit 100 ns molecular dynamics simulation, and end-point binding free energy calculations, the selected natural compounds were marked for substantial stability with PD-L1 via intermolecular interactions (hydrogen and hydrophobic) with essential residues in comparison to the JQT inhibitor. Collectively, the calculated results advocate the selected natural compounds as the putative potent inhibitors of PD-L1 and, therefore, can be considered for further development of PD-L1 immune checkpoint inhibitors in cancer immunotherapy.

• Klíčová slova
• Neoenactin B1, immunotherapy, molecular dynamics simulation, natural products, programmed death ligand 1,
• Publikační typ
• časopisecké články MeSH

PURPOSE: To detect the expression of programmed death-ligand 1 (PD-L1) in Merkel cell carcinoma (MCC) and to determine the prognostic influence of the PD-L1 expression. METHODS: A total of 13 patients with MCC were retrospectively evaluated (12 patients with primary skin lesion, one patient was diagnosed as unknown primary MCC). All patients underwent surgical resection. PD-L1 was determinated by imunohistochemistry. Immunostaining results were evaluated semiquantitatively. The prognostic influence of the expression of PD-L1 on overall survival (OS) was calculated with the Kaplan-Meier method and log-rank test. RESULTS: PD-L1 positivity was detected in 8 patients (61.5%), in all cases the result was 1+. PD-L1 negativity was shown in the remaining 5 patients. In patients with PD-L1 positivity median OS was 42.1 months (95% CI 9.3-42.1) compared with median OS of 9.4 months (95% CI 2.1-80.9) in the group of patients without PD-L1 positivity (p=0.417). CONCLUSIONS: PD-L1 positivity was found in 61.5% of patients with MCC. No prognostic significance of PD-L1 expression for OS was demonstrated.

• MeSH
• antigeny CD274 genetika   MeSH
• dospělí MeSH
• Kaplanův-Meierův odhad MeSH
• lidé středního věku MeSH
• lidé MeSH
• Merkelův nádor diagnóza   diagnostické zobrazování   genetika   patologie   MeSH
• přežití bez známek nemoci MeSH
• prognóza * MeSH
• regulace genové exprese u nádorů genetika   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• staging nádorů 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
• Názvy látek
• antigeny CD274 MeSH
• CD274 protein, human MeSH Prohlížeč

BACKGROUND: Immunotherapy blocking the PD-1/PD-L1 signalling pathway has become a dominant treatment modality for patients with non-small cell lung carcinoma (NSCLC). Programmed death-ligand 1 (PD-L1) expression on the membrane of tumour cells and/or tumour infiltrating lymphocytes (TIL) evaluated immunohistochemically is still the only clinically validated predictive biomarker for immunotherapy, but it has its limitations. TIL in the tumour microenviroment was identified as having predictive value. We retrospectively evaluated 134 NSCLC resection specimens, and analysed the association between PD-L1 expression, the presence of TIL, and the degree of desmoplasia in tumours. MATERIAL AND METHODS: PD-L1 expression on tumour cells and TIL were evaluated immunohistochemically using the anti-PD-L1 antibody (clone 22C3) and the anti-CD3 antibody (polyclone), respectively. PD-L1 was scored using the “tumour proportion score” (TPS) system with three categories: TPS < 1%, 1-49%, and 50%. TIL were evaluated semiquantitatively using the “percentage of stromal TIL” (PST) system, and categories of PST < 10%, 10-49% and 50% were recorded. The association between PD-L1 expression in tumour cells and TIL was compared with the PST value. Statistical analysis was conducted using the Cochran-Armitage test, and a p-value < 5% was considered significant. RESULTS: PD-L1 expression was significantly higher in PST 10-49% and 50% categories than in the PST < 10% category in grade 1 and grade 2 adenocarcinomas (p = 0.008), grade 3 adenocarcinomas (p = 0.009), and squamous cell carcinomas (p = 0.028). PD-L1 expression in TIL was associated with the PST value in squamous cell carcinomas (p = 0.025) but not in adenocarcinomas. Desmoplastic tumours had particularly low TPS and PST values. CONCLUSION: PD-L1 expression in NSCLC is associated with the presence of TIL. Desmoplastic areas in tumours represent immunologically inactive tumour microenviroments. Administration of anti-PD-1/PD-L1 immunotherapy, together with agents blocking the TGF-β signalling pathway, represent a promising combinational therapy for patients with desmoplastic NSCLC. The authors declare they have no potential confl cts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers. Submitted: 25. 11. 2019 Accepted: 8. 12. 2019.

• Klíčová slova
• non-small cell lung carcinoma, predictive biomarker, programmed death-ligand 1, tumour infiltrating lymphocytes,
• MeSH
• adenokarcinom metabolismus   MeSH
• antigeny CD274 metabolismus   MeSH
• biopsie MeSH
• lidé MeSH
• nádory plic metabolismus   patologie   MeSH
• nemalobuněčný karcinom plic metabolismus   patologie   MeSH
• stupeň nádoru MeSH
• tumor infiltrující lymfocyty metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antigeny CD274 MeSH
• CD274 protein, human MeSH Prohlížeč

INTRODUCTION: Recent studies on check-point inhibitor therapy, which seems to improve the prognosis of patients with advanced non-small cell lung carcinoma increase the importance of immunohistochemical analyses of the programmed-death receptor and of its ligand, PD-L1 protein. MATERIAL AND METHODS: In our study we present results of PD-L1 immunohistochemical tumor cell expression in a series of 325 lung carcinoma patients biopsies, using the clone 22C3 (and DAKO Link 48 immunostainer). Evaluation of the expression using tissue proportion scoring system allowed to distinguish negative cases (either 0 % or < 1 % of positive tumor cells) versus positive cases in the categories 1-9 %, 10-49 % and ≥ 50 % of positive tumor cells. RESULTS: In association to histopathologic parameters we observed similar rates of positive expression in patients with adenocarcinoma types (47,8 % of all the cases) as well as with squamous cell carcinomas (44,4 %). Within these histological categories, the rates of positivity were similar also in patients with small versus large (resectional) biopsies. In the biopsies of patients with adenocarcinoma we identified differences in the PD-L1 protein expression associated with its histological subtype. In the cases with predominant lepidic pattern the PD-L1 positivity was present in 18,8 %, with predominant acinar or papillary pattern in 40,8 % and in cases with predominant solid or micropapillary component in 74,1 % of the cases resp. Keratinizing squamous cell carcinomas were positive in 38,5 % and non-keratinizing in 53,8 % of all the cases. The hiqhest incidence of an extensive posivity was observed in sarcomatoid carcinoma type. DISCUSSION AND CONCLUSION: Immunohistochemically verified PD-L1 protein expression represents a broadly accepted predictive biomarker for immunotherapy of NSCLC patients. The indicated differences of the expression among various NSCLC types and subtypes require to be verified in larger cohorts of patients in relation with clinical parameters to demonstrate whether it could be plausible to use the PD-L1 expression in a role of a negative prognostic parameter.

• Klíčová slova
• programmed death-ligand 1 - non-small cell lung cancer - immunotherapy - prognostic marker.,
• MeSH
• antigeny CD274 * analýza   MeSH
• lidé MeSH
• nádorové biomarkery MeSH
• nádory plic * diagnóza   patologie   MeSH
• nemalobuněčný karcinom plic * diagnóza   patologie   MeSH
• prognóza MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antigeny CD274 * MeSH
• nádorové biomarkery MeSH