This is an overview of current problematics regarding the role of tumor infiltrating lymphocytes (TILs) in malignant melanomas. Various and often conflicting data have been published, correlating tumor type, stage, prognosis, as well as sex and age of patients. This is partly due to heterogeneity in scaling systems and unstandardized TILs grading but also due to changes of tumor-host interactions. Melanomas are an immunologically heterogeneous group with variability of TILs, where distinct gene expression patterns were found in tumors with absent, and/or non- brisk TIL grade versus brisk TIL grade. However, the presence of TILs alone appears to be inadequate for implicating them as immunologically functional. Further characterisation of TIL phenotype and function is warranted. This especially concerns, evaluation of TILs of the suppressor phenotype but rather than as a prognostic factor, more for prediction of targeted immunotherapy.

• Klíčová slova
• immune check point, melanoma, regulatory lymphocytes, tumor infiltrating lymphocytes,
• MeSH
• lidé MeSH
• melanom etiologie   patologie   MeSH
• nádory kůže etiologie   patologie   MeSH
• tumor infiltrující lymfocyty fyziologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

AIM: The aim of the present study was to investigate tumor-infiltrating leukocytes in patients with endometrial carcinoma. PATIENTS AND METHODS: Cluster of differentiation (CD)3(+), CD8(+) and C20(+) tumor-infiltrating lymphocytes (TILs) and CD68(+) tumor-associated macrophages (TAMs) were evaluated retrospectively by immunohistochemistry in tumor specimen from 124 patients with endometrial carcinoma. RESULTS: A significant decrease of CD3(+) TILs and an increase of CD68(+) TAM count was associated with higher tumor stage. In patients with early-stage, high-risk tumors, low intraepithelial CD3(+) TIL counts were associated with significantly inferior survival. In multivariate analysis of patients with early-stage tumors, intraepithelial CD3(+) TIL counts were an independent predictor of survival. CONCLUSION: In patients with endometrial carcinoma a decrease of intraepithelial CD3(+) TIL counts is associated with advanced stage and high risk group. Intraepithelial CD3(+) TIL counts are an independent predictor of survival in patients with early tumors.

• Klíčová slova
• Biomarkers, endometrial carcinoma, tumor-associated macrophages, tumor-infiltrating lymphocytes,
• MeSH
• antigeny CD3 metabolismus   MeSH
• leukocyty imunologie   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory endometria imunologie   mortalita   patologie   chirurgie   MeSH
• počet buněk MeSH
• prognóza MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• staging nádorů MeSH
• stupeň nádoru MeSH
• tumor infiltrující lymfocyty imunologie   metabolismus   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antigeny CD3 MeSH

Despite the progress of tailored therapeutic strategies in patients with breast cancer, there is an unmet medical need for additional biomarkers that would guide therapy, including the administration of targeted agents. It has been demonstrated that the presence of tumor-infiltrating lymphocytes (TILs) is associated with prognosis in patients with early breast cancer. Moreover, TIL counts were shown to predict outcome of neoadjuvant chemotherapy. The neoadjuvant setting is increasingly used to assess the efficacy of new systemic therapies, and TILs are promising as a biomarker reflecting the immune response to tumor. Future studies should investigate on the integration of TILs as predictive biomarkers in patients treated with targeted- agents.

• Klíčová slova
• Breast cancer, review, targeted therapy, tumor-infiltrating lymphocytes,
• MeSH
• lidé MeSH
• nádory prsu diagnóza   imunologie   terapie   MeSH
• neoadjuvantní terapie * MeSH
• prognóza MeSH
• tumor infiltrující lymfocyty imunologie   patologie   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

The evaluation of inflammatory infiltrate (tumor infiltrating lymphocytes - TIL) should be a standard part of biopsy examination for malignant melanoma. Currently, the most commonly used assessment method according to Clark is not optimal and there have been attempts to find an alternative system. Here we present an overview of possible approaches involving five different evaluation methods based on hematoxylin-eosin staining, including the recent suggestion of unified TIL evaluation method for all solid tumors. The issue of methodology, prognostic and predictive significance of TIL determination as well as the importance of immunohistochemical subtyping of inflammatory infiltrate is discussed.

• Klíčová slova
• malignant melanoma - tumor infiltrating lymphocytes - prediction - prognosis.,
• MeSH
• biopsie MeSH
• lidé MeSH
• melanom * imunologie   terapie   MeSH
• nádory kůže * imunologie   terapie   MeSH
• prognóza MeSH
• tumor infiltrující lymfocyty * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Evaluation of tumor infiltrating lymphocytes (TIL) is gaining importance in many cancers not only because of their prognostic, but also predictive significance. One of the tumors in which the evaluation of TIL is of prognostic importance and has potential predictive impact on the modification of treatment procedures is breast cancer, especially its so-called triple negative, and HER2 positive variants.The aim of this review is to provide an overview of the issue of TIL evaluation in breast cancer, focusing not only on the clinical significance of this evaluation, but especially on the methodological aspects of evaluation and standardized reporting of the results.

• Klíčová slova
• Prognosis, breast cancer, cervical length measurement, heart failure, prediction, tumor infiltrating lymphocytes,
• MeSH
• lidé MeSH
• nádory prsu * diagnóza   MeSH
• prognóza MeSH
• receptor erbB-2 MeSH
• triple-negativní karcinom prsu * MeSH
• tumor infiltrující lymfocyty MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• receptor erbB-2 MeSH

BACKGROUND: The tumor microenvironment plays an important role in tumorigenesis and the tumor-host relationship. An important part of the tumor microenvironment is inflammatory infiltration. Its evaluation in solid tumors has prognostic meaning and appears also to be predictive of outcome, which is particularly important for predicting responses to immune checkpoint inhibitors. However, the methodology used to assess inflammatory infiltration is problematic, because it has been standardized only for certain types of tumors. OBJECTIVE: The present study provides an overview of current issues related to the evaluation of inflammatory cells (tumor infiltrating lymphocytes) in solid tumors, specifically in tumors of the breast, lung, head and neck, gastrointestinal tract, female genital tract, urogenital tract, brain, malignant mesothelioma, and malignant melanoma. Various methodologies for evaluation are mentioned, including the efforts that are being made to standardize these methodologies and the importance of immunophenotyping inflammatory infiltrates. With regard to clinical meaning, prognostic and predictive significance are also discussed. CONCLUSION: The evaluation of TILs in solid tumors often has predictive value; however, the results have been equivocal. There is also ambiguity about the predictive use of this marker. Despite all the methodological developments, which have resulted in the implementation of complicated technologies (image analysis, multiplex fluorescence immunohistochemistry, and mass spectrometry) for the evaluation of the various aspects of inflammatory infiltrates present in tumors, including their functional characteristics, there is still a need for standardization and development of inexpensive and universally available methodologies to enable the wide use of TIL evaluations in clinical settings. The recently proposed unified methodology may be used in all solid tumors and could help resolve one of the main limitations of the routine use of TIL, i.e., the inconsistent approach to assessment.Key words: solid tumors - tumor-infiltratig lymphocytes - inflammatory cells This work was supported by program of the Czech Ministry of Health No. RVO-VFN 64165 and AZV project No. 16-30954A, Charles University and OPPK (CZ.2.16/3.1.00/24509). The authors declare they have no potential conflicts 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: 24. 9. 2017Accepted: 3. 10. 2017.

• MeSH
• lidé MeSH
• nádory imunologie   MeSH
• tumor infiltrující lymfocyty imunologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Our knowledge of tumor-infiltrating lymphocytes (TILs) is dramatically expanding. These cells have proven prognostic and therapeutic value for many cancer outcomes and potential to treat also disseminated breast, colorectal, or lung cancer. However, the therapeutical outcome of TILs is negatively affected by tumor mutational burden and neoantigens. On the other hand, it can be improved in combination with checkpoint blockade therapy. This knowledge and rapid detection techniques alongside gene editing allow us to classify and modify T cells in many ways. Hence, to tailor them precisely to the patient´s needs as to program T cell receptors to recognize specific tumor-associated neoantigens and to insert them into lymphocytes or to select tumor neoantigen-specific T cells, for the development of vaccines that recognize tumor-specific antigens in tumors or metastases. Further studies and clinical trials in the field are needed for an even better-detailed understanding of TILs interactions and aiming in the fight against multiple cancers.

• MeSH
• antigeny nádorové genetika   MeSH
• imunoterapie adoptivní metody   MeSH
• kolorektální nádory * terapie   MeSH
• lidé MeSH
• nádory plic * terapie   MeSH
• T-lymfocyty MeSH
• tumor infiltrující lymfocyty MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• antigeny nádorové MeSH

The objective of our study was to compare the five different scoring methods of tumor-infiltrating lymphocytes (TILs) assessment in a group of 213 cases of superficial spreading and nodular melanoma. The scoring methods include (a) Clark scoring; (b) Melanoma Institute Australia system; (c) scoring system used in the study of Saldanha et al.; (d) scoring system used in the TCGA study and modified by Park et al.; and (e) the system recently proposed by the "International Immuno-Oncology Biomarker Working Group" for TILs scoring in all solid tumors. Prediction of survival with three main outcomes-disease-specific-free survival, local recurrence-free survival, and distant metastasis-free survival-was evaluated. The prognostic value of TILs showed statistical significance in univariate analysis regarding all three of the outcomes only for three of the five evaluated methods; the Clark scoring, the Melanoma Institute Australia system, and the system proposed by the "International Immuno-Oncology Biomarker Working Group". However, in multivariate analysis with covariants including Breslow thickness, type of melanoma, location, sex, and age, we did not find TILs to be an independent prognostic factor.

• Klíčová slova
• nodular melanoma, prognosis, superficial spreading melanoma, tumor-infiltrating lymphocytes,
• MeSH
• dospělí MeSH
• dvojitá slepá metoda MeSH
• lidé středního věku MeSH
• lidé MeSH
• melanom klasifikace   imunologie   patologie   MeSH
• mladiství MeSH
• mladý dospělý MeSH
• nádory kůže imunologie   patologie   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• tumor infiltrující lymfocyty imunologie   MeSH
• výzkumný projekt MeSH
• zánět imunologie   patologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND: We aimed to assess the prognostic value of tumor infiltrating lymphocytes (TILs) in patients with bladder cancer (BC) after radical cystectomy (RC). MATERIALS AND METHODS: We searched Pubmed, Web of Science and Scopus in April 2022 to identify studies assessing the prognostic value of TILs, including a subset of lymphocytes (eg, CD3, CD8, FOXP3), after RC. The endpoints were overall survival and recurrent free survival. Subgroup analyses were performed based on the evaluation method for TILs (ie, CD3, CD8, FOXP3, HE staining). RESULTS: Overall, 9 studies comprising 1413 patients were included in this meta-analysis. The meta-analysis revealed that elevated expressions of TILs were significantly associated with favorable OS (pooled hazard ratio [HR]: 0.65, 95% confidence interval [CI]: 0.51-0.83) and RFS (pooled HR: 0.48, 95% CI: 0.35-0.64). In subgroup analyses, high CD8+ TILs were also associated with favorable OS (HR: 0.51, 95% CI: 0.33-0.80) and RFS (pooled HR: 0.53, 95% CI: 0.36-0.76). Among 3 studies comprising 146 patients, high intratumoral TILs were significantly associated with favorable OS (pooled HR: 0.34, 95% CI: 0.19-0.60). CONCLUSION: TILs are useful prognostic markers in patients treated with RC for BC. Although the prognostic value of TILs is varied, depending on the subset and infiltration site, CD8+ TILs and intratumoral TILs are associated with oncologic outcomes. Further studies are warranted to explicate the predictive value of TILs on the response to perioperative systemic therapy to help clinical decision-making in patients with BC.

• Klíčová slova
• MIBC, TIL,
• MeSH
• cystektomie MeSH
• forkhead transkripční faktory metabolismus   MeSH
• lidé MeSH
• nádory močového měchýře * patologie   MeSH
• prognóza MeSH
• tumor infiltrující lymfocyty * metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• systematický přehled MeSH
• Názvy látek
• forkhead transkripční faktory MeSH

Tumor-infiltrating leukocytes and other immunohistochemical parameters were evaluated in pretherapeutic biopsies and resection specimens in 73 patients undergoing neoadjuvant chemotherapy with doxorubicin and paclitaxel. Ten patients with pathological complete response had significantly higher p53 expression, CD3(+) lymphocyte and CD83(+) cell counts, and lower progesterone receptor expression. In the remaining 63 patients, a significant decrease in the percentage of Ki-67, vascular endothelial growth factor expression, CD68(+) monocytes, and increased CD31(+), CD34(+), and SMA(+) stromal vessels, maximal CD3(+) and CD56(+) lymphocyte, maximal and mean CD83(+) cell, maximal CD1a(+), and maximal and mean S100(+) cell counts were observed after neoadjuvant chemotherapy.

• MeSH
• antigen Ki-67 analýza   MeSH
• CD antigeny analýza   MeSH
• dospělí MeSH
• imunohistochemie MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• nádorové biomarkery analýza   MeSH
• nádory prsu farmakoterapie   patologie   MeSH
• neoadjuvantní terapie metody   MeSH
• počet lymfocytů MeSH
• prediktivní hodnota testů MeSH
• senioři MeSH
• staging nádorů MeSH
• tumor infiltrující lymfocyty patologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antigen Ki-67 MeSH
• CD antigeny MeSH
• nádorové biomarkery MeSH