Guido Klode

Guido Klode Witze aus der Salatschleuder:"Lilli" lässt Breitenbach lachen

Martin Lüker & Guido Klode (Tante Lilli). Prädikat: Zauberhaft! Anders kann man dieses energiereiche Musik-Comedy-Duo nicht beschreiben. Und zum. Guido Klode ist bei Facebook. Tritt Facebook bei, um dich mit Guido Klode und anderen Nutzern, die du kennst, zu vernetzen. Facebook gibt Menschen die. Guido Klode alias Lilli c/o. MPR-Promotion Auf den Siechen 2b Kassel. Umsatzsteuer-Identifikationsnummer gemäß §27 a Umsatzsteuergesetz. Guido Klode & Martin Lüker. Alle Jahre Mieder tobt der Weihnachtswahnsinn durch die deutschen Wohnzimmer und Lilli & Herr Lüker mischen mit. Die beiden​. Am Tag darauf lud dann Guido Klode alias „Tante Lilli“ zum Kaffeeklatsch. Hohenhameln. Gleich zwei Vorstellungen an einem Wochenende.

Guido Klode

Melden Sie sich für den Guido Klode Ticketalarm an und Tickets für Guido Klode bei Eventim sichern! Lilli“ alias Guido Klode hat mit Witzen am laufenden Band das Publikum auf der Hermannsbühne in Breitenbach bestens unterhalten. Ticketalarm Guido Klode: jetzt anmelden und benachrichtigt werden, sobald es Tickets für Guido Klode auf american-crush.co gibt.

Plots were drawn using ggplot2 package in R. The curve was smoothened using a linear regression lm. Out of 74 intracranial melanoma metastases from the 72 patients, 48 metastases were located in the cerebrum and six tumors were resected from the cerebellum, while information on supra- vs.

First, we detected cytoplasmic IDO expression in all 74 intracranial and 22 extracranial metastases of advanced melanoma patients Figure 1.

Interestingly, we observed distinct patterns of IDO tissue distribution. Immunohistochemical and pathological analyses of IDO distribution in human melanoma metastases.

Four distinct infiltration patterns of IDO-positive cells were predominantly detected independent of intracranial or extracranial origin.

Representative images for the individual distribution patterns are presented in intracranial metastases.

In addition to the distinct patterns of IDO immunopositivity in malignant melanoma metastases, we detected also an intratumoral heterogeneity for the IDO expression intensity, independent of the tissue origin Supplementary Figure 1.

By using quantitative digital pathology tissue diagnostics, we generated an individual cell-by-cell threshold for the immunohistochemistry-based IDO intensity level Figure 2A.

However, Kaplan-Meier analysis revealed that neither the IDO expression level nor the total number of IDO-positive cells in the distinct metastases impacted disease progression or survival of advanced melanoma patients data not shown.

Quantitative assessment of IDO-expression intensity in patient-matched melanoma metastases of intracranial and corresponding extracranial origin.

A Representative images for immunohistochemical-based IDO-expression left , parameter-based separation of cell-cell borders middle , classification of high brown , moderate orange and low yellow expression intensities or IDO-negative areas white, right.

Tukey HSD test was performed to test for significance. The current knowledge and understanding of cancer immunotherapy has changed dramatically during the last decades.

Multiple clinical data let assume that the amount and also the localization of the lymphocytic infiltrate in different cancer entities directs the response to cancer immunotherapy.

Interestingly, we found that the localization of IDO-positive cells is strongly paralleled with the localization of the lymphocytic infiltrate, with exception of FoxP3-positive regulatory T cells, which were also recruited into the tumor mass, but not localized in areas of high IDO-expression as exemplarily presented in Supplementary Figure 2 in cutaneous melanoma metastases.

Quantitative assessment for the number of immunoreactive cells in patient-matched melanoma metastases. Comparative analyses of intratumoral and peritumoral IDO-expression in human melanoma metastases of intracranial and extracranial origin.

To ensure statistical balance between both parameters we excluded all patient samples from the analyses in the case of missing stroma in the individual tissue specimen.

The development of brain metastases is a significant cause of morbidity or mortality for patients with metastatic cancer, including melanoma.

However, for still unclear clinical reasons some patients show a better outcome as others. By using a total of 38 cases, 13 patients who received standard care therapy and 17 cases which received immune checkpoint inhibitors alone or in combination with other therapies, showed a median survival of vs.

Therefore, we asked whether the expression of IDO itself, independent of the cellular source, is associated with the recruitment of tumor infiltrating lymphocyte subsets and whether this immunoreactive infiltrate influences the clinical outcome of melanoma patients in our cohort.

However, preforming a multivariate Cox proportional hazards regression model we did not observe a significant association for disease progression with regard to the individual lymphocyte subtypes in metastases of the brain Supplementary Figure 3.

Correlation of the immunoreactive infiltrate and IDO expression in extracranial and intracranial melanoma metastases.

Each dot in the scatter plot represents an individual patient. Spearman correlations were performed and regression was calculted using lm function.

Hazard ratio Overall survival. Forest plot for the cox proportional hazards model was calculated by using age, gender, localization of the ICM and immunoreactive infiltrates.

According to the multivariate model, low PD-L1 expressing patients have a significantly higher hazards ratio and thus poor overall survival compared to patients with high PD-L1 expression.

A Kaplan-Meier survival analysis was performed and the patients were divided in two groups based on median PD-L1 expression.

However, due to the limited number of patients, these results must be validated in a larger cohort of advanced melanoma patients with brain metastases undergoing checkpoint therapy.

Disease progression and survival analyses of melanoma patients under immunotherapy with respect to intracranial PD-L1 expression. A Progression-free survival.

Long-rank test statistics show no differences in the progression-free survival for patients with high and low PD-L1 expression Log-rank p -value 0.

B Overall survival. According to the Kaplan—Meier curve patients with high PD-L1 had a greater benefit from immunotherapy and showed a better overall survival Log-rank p -value 0.

In addition to tumor cells, expression of the immunomodulatory protein IDO by subpopulations of tumor-associated immune cells, e.

However, the major cellular source of IDO expression in intracranial melanoma metastases is still unknown. To avoid false positive detection mediated by brownish melanophages or melanocytic tumor cells, we exclusively selected amelanotic tissue samples for these analyses.

Nevertheless, it is important to note that all of these markers are also expressed by different subpopulations of monocytes and granulocytes, dependent on their level of maturation and activation.

IDO-expression on cellular components of the immunoreactive tumor infiltrate in melanoma metastases of the central nervous system.

Representative images were presented. Following non-small cell lung cancer NSCLC and breast cancer, melanoma is the third most common origin of metastases to the brain.

Despite recent advances in the systemic treatment of extracranial metastases by using BRAF-targeted therapy in patients harboring BRAF VE -mutant melanomas or inhibitors targeting immune checkpoint molecules, the treatment of melanoma brain metastases remains a major challenge.

Multiple phase II and III studies have shown that ipilimumab and nivolumab are active in advanced melanoma and that the combination therapies involving PD-1 or CTLA-4 inhibitors presented a superior efficacy when compared to the individual monotherapies 50 — After extravasation of tumor cells into the brain parenchyma they enter a fundamentally different tissue environment with respect to the metabolic situation, the cellular compositions, the brain-specific extracellular matrix proteins and the immunoreactive heterogenous cell population with regard to the primary site of their origin This appears particularly relevant in the context of immune cell activity against extravasated single cancer cells and micrometastases when the normal brain parenchyma, including the blood-brain barrier, is still largely intact.

In line with this concept, melanoma patients developed remarkable high rates of BM during Ipilimumab in one study 57 , which fits to the empirical impression of many clinical experts in the field.

In contrast, brain macrometastases have been found to respond well to ipilimumab and other immune checkpoint inhibitors in subsets of patients 35 , 58 which supports the general concept that preventing metastatic outgrowth is very different biologically and therapeutically from targeting large established macrometastases.

However, limited clinical data are available adressing the activation of checkpoint inhibitors in the CNS. One of the first phase II studies evaluated the activity of ipilimumab in patients with melanoma brain metastases and enrolled 72 patients in a two-arm clinical trial Fifty-one patients were neurologically asymptomatic and therefore did not receive any corticosteroids at time of enrollment arm A , whereas 21 patients showed symptomatic disease and were on a stable dose of corticosteroids arm B.

In summary, all achieved activities at the intracranial site, albeit to limited extents. These clinical data argue for a principle ability of immune checkpoint inhibitors to reach meaningful anticancer immunity in the brain, however, the current therapies seem to fail for their suppression of metastatic seeding of the CNS by cancer cells.

IDO expression and activity has been documented in several cancer entities and has been correlated with negative prognostic factors 9.

In the present study, we analyzed tissue samples of 74 intracranial metastases from 72 advanced melanoma patients and 22 matched melanoma metastases at extracranial sites from 19 of the 72 patients.

We specifically adressed the expression of immunosuppressive mediators such as IDO and PD-L1 in the context of the tumor-associated immunoreactive infiltrate.

We found that IDO is expressed in different patterns in melanoma brain metastases indicating IDO expression as a marker of anti-tumor immune response.

First, in contrast to data described by Krähenbühl et al. Moreover, a strong correlation of IDO expression in peritumoral sites of the primary tumors has been linked to IDO expression in the sentinel lymph node, directing the numbers of intratumoral lymphocytes as a result of immune control In addition, our investigation revealed different distribution patters of IDO-positive cells in melanoma metastases, but these were independent of the metastatic origin.

Interestingly, neither the localization nor the distribution pattern of IDO had an impact on patient outcome. However, the heterogeneous expression of the immunosupressive IDO which we detected both, within and between patients, may explain the high variation in the clincal response to IDO combination treatment 19 , 63 , Since several studies correlated high TIL levels with favorable outcome 67 — 69 our data are in line with the work of Harter et al.

Neither disease progression nor patient survival was affected by the number of TILs in melanoma brain metastases in our patient cohort per se.

Nevertheless, we need to consider that our cohort consists of patients who had received various mono- or combination therapies before resection of the investigated brain metastasis, possibly including pre-operative corticosteroid treatment, to minimize inflammatory side effects.

Therefore, we are aware of the discussion that patient's therapy may affect the cellular component of immunoreactive populations, however, it has been shown that corticosteroids neither affect the TIL population nor the PD-L1 expression in melanoma brain metastases However, melanoma brain metastases do not appear to show this reciprocal interplay.

The heterogenous IDO expression of melanoma metastases which we described here on the basis of immunohistochemistry, prompted our further investigation on the cell types that represent the major producers of IDO in melanoma brain metastases.

Despite functional knowledge of myeloid cells, e. In general, microglia and TAMs represent the most abundant non-neoplastic cells in brain metastases Despite the lack of clinical data for the impact of microglia density and brain-associated TAM infiltration for patients prognosis, some pre-clinical data implicate tumor-promoting functions 74 — In addition, functional charaterization of IDO expression with regard to polarization and functionality of both cell types in brain metastases are missing so far.

These newly identified surface markers could represent potential novel targets to reach more meaningful activity with regard to melanoma immunotherapy, potentially including re-education of macrophages as a new therapeutic strategy DH-R and SM performed the experiments, generated, and analyzed data.

SM and BB conceptualized and generated statistical analyses. GR and IH designed the selection of the patient cohort.

IH conceptualized, coordinated, and directed the project. All authors performed manuscript review.

GR has received research grants from Roche and Merck, as well as honoraria for advisory boards from Abbvie.

The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Konstanze Wegener Stiftung all to IH. National Center for Biotechnology Information , U. Journal List Front Immunol v.

Front Immunol. Published online Feb 5. Sadaf S. Author information Article notes Copyright and License information Disclaimer.

This article was submitted to Cancer Immunity and Immunotherapy, a section of the journal Frontiers in Immunology.

Received Sep 3; Accepted Jan The use, distribution or reproduction in other forums is permitted, provided the original author s and the copyright owner s are credited and that the original publication in this journal is cited, in accordance with accepted academic practice.

No use, distribution or reproduction is permitted which does not comply with these terms. TIF 1.

TIF 9. TIF K. Abstract The manifestation of brain metastases in patients with advanced melanoma is a common event that limits patient's survival and quality of life.

Keywords: melanoma, brain metastases, IDO, immune checkpoint molecules, tumor-associated macrophages, immunogenic microenvironment.

Introduction The recent clinical success of cancer immunotherapies in patients suffering from malignant melanoma and other cancer types has revolutionized the therapeutic landscape of metastatic cancer.

Table 1 Patients characteristics and clinical data. Open in a separate window. Immunohistochemistry Serial sections were prepared from formalin-fixed, paraffin-embedded tumor biopsy samples.

Statistical Analysis All statistical analyses were performed in R version 3. Figure 1. Figure 2. Figure 3.

Figure 4. Figure 5. Figure 6. Figure 7. Figure 8. Discussion Following non-small cell lung cancer NSCLC and breast cancer, melanoma is the third most common origin of metastases to the brain.

Data Availability Statement The datasets generated for this study are available on request to the corresponding author.

Ethics Statement Informed patient consent was obtained from all patients. Conflict of Interest GR has received research grants from Roche and Merck, as well as honoraria for advisory boards from Abbvie.

Acknowledgments We gratefully acknowledge I. Westedt and M. Bau for the technical assistance. Footnotes Funding.

Click here for additional data file. References 1. Ribas A. Tumor immunotherapy directed at PD N Engl J Med. Ribas A, Wolchok JD.

Cancer immunotherapy using checkpoint blockade. PD-1 blockade induces responses by inhibiting adaptive immune resistance.

Interferons, immunity and cancer immunoediting. Nat Rev Immunol. Trends Immunol. The dark side of IFN-gamma: its role in promoting cancer immunoevasion.

Int J Mol Sci. Relationship between interferon-gamma, indoleamine 2,3-dioxygenase, and tryptophan catabolism.

Sci Transl Med. The rationale of indoleamine 2,3-dioxygenase inhibition for cancer therapy. Eur J Cancer. J Immunother Cancer. Host indoleamine 2,3-dioxygenase: contribution to systemic acquired tumor tolerance.

Immunol Invest. J Immunol. Potential regulatory function of human dendritic cells expressing indoleamine 2,3-dioxygenase.

Peritumoral indoleamine 2,3-dioxygenase expression in melanoma: an early marker of resistance to immune control?

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In addition to tumor cells, expression of the immunomodulatory protein IDO by subpopulations of tumor-associated immune cells, e. However, the major cellular source of IDO expression in intracranial melanoma metastases is still unknown.

To avoid false positive detection mediated by brownish melanophages or melanocytic tumor cells, we exclusively selected amelanotic tissue samples for these analyses.

Nevertheless, it is important to note that all of these markers are also expressed by different subpopulations of monocytes and granulocytes, dependent on their level of maturation and activation.

IDO-expression on cellular components of the immunoreactive tumor infiltrate in melanoma metastases of the central nervous system.

Representative images were presented. Following non-small cell lung cancer NSCLC and breast cancer, melanoma is the third most common origin of metastases to the brain.

Despite recent advances in the systemic treatment of extracranial metastases by using BRAF-targeted therapy in patients harboring BRAF VE -mutant melanomas or inhibitors targeting immune checkpoint molecules, the treatment of melanoma brain metastases remains a major challenge.

Multiple phase II and III studies have shown that ipilimumab and nivolumab are active in advanced melanoma and that the combination therapies involving PD-1 or CTLA-4 inhibitors presented a superior efficacy when compared to the individual monotherapies 50 — After extravasation of tumor cells into the brain parenchyma they enter a fundamentally different tissue environment with respect to the metabolic situation, the cellular compositions, the brain-specific extracellular matrix proteins and the immunoreactive heterogenous cell population with regard to the primary site of their origin This appears particularly relevant in the context of immune cell activity against extravasated single cancer cells and micrometastases when the normal brain parenchyma, including the blood-brain barrier, is still largely intact.

In line with this concept, melanoma patients developed remarkable high rates of BM during Ipilimumab in one study 57 , which fits to the empirical impression of many clinical experts in the field.

In contrast, brain macrometastases have been found to respond well to ipilimumab and other immune checkpoint inhibitors in subsets of patients 35 , 58 which supports the general concept that preventing metastatic outgrowth is very different biologically and therapeutically from targeting large established macrometastases.

However, limited clinical data are available adressing the activation of checkpoint inhibitors in the CNS. One of the first phase II studies evaluated the activity of ipilimumab in patients with melanoma brain metastases and enrolled 72 patients in a two-arm clinical trial Fifty-one patients were neurologically asymptomatic and therefore did not receive any corticosteroids at time of enrollment arm A , whereas 21 patients showed symptomatic disease and were on a stable dose of corticosteroids arm B.

In summary, all achieved activities at the intracranial site, albeit to limited extents. These clinical data argue for a principle ability of immune checkpoint inhibitors to reach meaningful anticancer immunity in the brain, however, the current therapies seem to fail for their suppression of metastatic seeding of the CNS by cancer cells.

IDO expression and activity has been documented in several cancer entities and has been correlated with negative prognostic factors 9.

In the present study, we analyzed tissue samples of 74 intracranial metastases from 72 advanced melanoma patients and 22 matched melanoma metastases at extracranial sites from 19 of the 72 patients.

We specifically adressed the expression of immunosuppressive mediators such as IDO and PD-L1 in the context of the tumor-associated immunoreactive infiltrate.

We found that IDO is expressed in different patterns in melanoma brain metastases indicating IDO expression as a marker of anti-tumor immune response.

First, in contrast to data described by Krähenbühl et al. Moreover, a strong correlation of IDO expression in peritumoral sites of the primary tumors has been linked to IDO expression in the sentinel lymph node, directing the numbers of intratumoral lymphocytes as a result of immune control In addition, our investigation revealed different distribution patters of IDO-positive cells in melanoma metastases, but these were independent of the metastatic origin.

Interestingly, neither the localization nor the distribution pattern of IDO had an impact on patient outcome. However, the heterogeneous expression of the immunosupressive IDO which we detected both, within and between patients, may explain the high variation in the clincal response to IDO combination treatment 19 , 63 , Since several studies correlated high TIL levels with favorable outcome 67 — 69 our data are in line with the work of Harter et al.

Neither disease progression nor patient survival was affected by the number of TILs in melanoma brain metastases in our patient cohort per se.

Nevertheless, we need to consider that our cohort consists of patients who had received various mono- or combination therapies before resection of the investigated brain metastasis, possibly including pre-operative corticosteroid treatment, to minimize inflammatory side effects.

Therefore, we are aware of the discussion that patient's therapy may affect the cellular component of immunoreactive populations, however, it has been shown that corticosteroids neither affect the TIL population nor the PD-L1 expression in melanoma brain metastases However, melanoma brain metastases do not appear to show this reciprocal interplay.

The heterogenous IDO expression of melanoma metastases which we described here on the basis of immunohistochemistry, prompted our further investigation on the cell types that represent the major producers of IDO in melanoma brain metastases.

Despite functional knowledge of myeloid cells, e. In general, microglia and TAMs represent the most abundant non-neoplastic cells in brain metastases Despite the lack of clinical data for the impact of microglia density and brain-associated TAM infiltration for patients prognosis, some pre-clinical data implicate tumor-promoting functions 74 — In addition, functional charaterization of IDO expression with regard to polarization and functionality of both cell types in brain metastases are missing so far.

These newly identified surface markers could represent potential novel targets to reach more meaningful activity with regard to melanoma immunotherapy, potentially including re-education of macrophages as a new therapeutic strategy DH-R and SM performed the experiments, generated, and analyzed data.

SM and BB conceptualized and generated statistical analyses. GR and IH designed the selection of the patient cohort.

IH conceptualized, coordinated, and directed the project. All authors performed manuscript review. GR has received research grants from Roche and Merck, as well as honoraria for advisory boards from Abbvie.

The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Konstanze Wegener Stiftung all to IH. National Center for Biotechnology Information , U. Journal List Front Immunol v.

Front Immunol. Published online Feb 5. Sadaf S. Author information Article notes Copyright and License information Disclaimer.

This article was submitted to Cancer Immunity and Immunotherapy, a section of the journal Frontiers in Immunology.

Received Sep 3; Accepted Jan The use, distribution or reproduction in other forums is permitted, provided the original author s and the copyright owner s are credited and that the original publication in this journal is cited, in accordance with accepted academic practice.

No use, distribution or reproduction is permitted which does not comply with these terms. TIF 1. TIF 9. TIF K. Abstract The manifestation of brain metastases in patients with advanced melanoma is a common event that limits patient's survival and quality of life.

Keywords: melanoma, brain metastases, IDO, immune checkpoint molecules, tumor-associated macrophages, immunogenic microenvironment.

Introduction The recent clinical success of cancer immunotherapies in patients suffering from malignant melanoma and other cancer types has revolutionized the therapeutic landscape of metastatic cancer.

Table 1 Patients characteristics and clinical data. Open in a separate window. Immunohistochemistry Serial sections were prepared from formalin-fixed, paraffin-embedded tumor biopsy samples.

Statistical Analysis All statistical analyses were performed in R version 3. Figure 1. Figure 2. Figure 3. Figure 4.

Figure 5. Figure 6. Figure 7. Figure 8. Discussion Following non-small cell lung cancer NSCLC and breast cancer, melanoma is the third most common origin of metastases to the brain.

Data Availability Statement The datasets generated for this study are available on request to the corresponding author. Ethics Statement Informed patient consent was obtained from all patients.

Conflict of Interest GR has received research grants from Roche and Merck, as well as honoraria for advisory boards from Abbvie.

Acknowledgments We gratefully acknowledge I. Westedt and M. Bau for the technical assistance. Footnotes Funding. Click here for additional data file.

References 1. Ribas A. Tumor immunotherapy directed at PD N Engl J Med. Ribas A, Wolchok JD. Cancer immunotherapy using checkpoint blockade.

PD-1 blockade induces responses by inhibiting adaptive immune resistance. Interferons, immunity and cancer immunoediting.

Nat Rev Immunol. Trends Immunol. The dark side of IFN-gamma: its role in promoting cancer immunoevasion.

Int J Mol Sci. Relationship between interferon-gamma, indoleamine 2,3-dioxygenase, and tryptophan catabolism. Sci Transl Med.

The rationale of indoleamine 2,3-dioxygenase inhibition for cancer therapy. Eur J Cancer. J Immunother Cancer. Host indoleamine 2,3-dioxygenase: contribution to systemic acquired tumor tolerance.

Immunol Invest. J Immunol. Potential regulatory function of human dendritic cells expressing indoleamine 2,3-dioxygenase.

Peritumoral indoleamine 2,3-dioxygenase expression in melanoma: an early marker of resistance to immune control? Br J Dermatol. Indoleamine 2,3-dioxygenase, a new prognostic marker in sentinel lymph nodes of melanoma patients.

Ann Oncol. Lancet Oncol. Incidence and prognosis of patients with brain metastases at diagnosis of systemic malignancy: a population-based study.

Neuro Oncol. A perspective on cancer cell metastasis. New era in the management of melanoma brain metastases.

Brain metastases from solid tumors: disease outcome according to type of treatment and therapeutic resources of the treating center.

J Exp Clin Cancer Res. Identifying early melanomas at higher risk for metastases. J Clin Oncol. Isolated cerebral susceptibility artefacts in patients with malignant melanoma: metastasis or not?

Eur Radiol. Intracerebral metastases of malignant melanoma and their recurrences—a clinical analysis. Clin Neurol Neurosurg.

Melanoma brain metastases: an unmet challenge in the era of active therapy. Curr Oncol Rep. Dabrafenib in patients with melanoma, untreated brain metastases, and other solid tumours: a phase 1 dose-escalation trial.

Melanoma staging: evidence-based changes in the American Joint Committee on Cancer eighth edition cancer staging manual. CA Cancer J Clin.

A dural lymphatic vascular system that drains brain interstitial fluid and macromolecules. J Exp Med. Structural and functional features of central nervous system lymphatic vessels.

Immune privilege of the CNS is not the consequence of limited antigen sampling. Sci Rep. Flt3L controls the development of radiosensitive dendritic cells in the meninges and choroid plexus of the steady-state mouse brain.

Nat Clin Pract Oncol. Berghoff AS, Preusser M. The inflammatory microenvironment in brain metastases: potential treatment target?

Chin Clin Oncol. Tumour-infiltrating lymphocytes and expression of programmed death ligand 1 PD-L1 in melanoma brain metastases.

Ipilimumab in patients with melanoma and brain metastases: an open-label, phase 2 trial. Pembrolizumab for patients with melanoma or non-small-cell lung cancer and untreated brain metastases: early analysis of a non-randomised, open-label, phase 2 trial.

Immune-related tumor response dynamics in melanoma patients treated with pembrolizumab: identifying markers for clinical outcome and treatment decisions.

Clin Cancer Res. Combination nivolumab and ipilimumab or nivolumab alone in melanoma brain metastases: a multicentre randomised phase 2 study.

Peritumoral endothelial indoleamine 2, 3-dioxygenase expression is an early independent marker of disease relapse in colorectal cancer and is influenced by DNA mismatch repair profile.

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