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P. Pauwels
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OA02 - Novel Targets and Biomarkers in Malignant Pleural Mesothelioma (ID 369)
- Event: WCLC 2016
- Type: Oral Session
- Track: Mesothelioma/Thymic Malignancies/Esophageal Cancer/Other Thoracic Malignancies
- Presentations: 1
- Moderators:L.E. Raez, M. Jakopovic
- Coordinates: 12/05/2016, 11:00 - 12:30, Stolz 2
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OA02.07 - Characterization of the Tumor Microenvironment and Investigation of Immune Checkpoint Expression in Malignant Pleural Mesothelioma (ID 4437)
11:00 - 12:30 | Author(s): P. Pauwels
- Abstract
- Presentation
Background:
Malignant pleural mesothelioma (MPM) is an aggressive cancer with a poor prognosis and an increasing incidence, for which novel therapeutic strategies are urgently required. Since the immune system has been described to play a role in protection against MPM, characterization of its tumor immune microenvironment (TME) and immune checkpoints might help to identify new immunotherapeutic targets and their predictive and/or prognostic value.
Methods:
Immunohistochemistry (IHC) was performed on tissue samples of untreated (n=40) and chemotherapy-pretreated (n=14) MPM patients. Different subsets if immune cells were identified based on staining for CD4, CD8, FoxP3, CD68, CD45RO and granzyme B. The expression of the immune checkpoints TIM-3, LAG-3, PD-1 and its ligand PD-L1 was also investigated. The relationship between the immunological parameters and survival, as well as response to chemotherapy was analyzed using the R statistical software.
Results:
All patients had CD8+ tumor infiltrating lymphocytes (TILs), CD68+ histiocytes and macrophages and CD45RO+ T cells in their stroma, with CD8+ TILs being the predominant cell type of the immune infiltrate. Stromal CD4+ TILs were found in 75% of the untreated and 71% of the pretreated samples. A subset of those cells was also FoxP3+ and these CD4+FoxP3+ cells were positively correlated with stromal CD4 expression (p<0.001). Less than half of the samples showed positivity for granzyme B. Both, untreated and pretreated patients had PD-1+ TILs, while only 10% of the untreated patients also had PD-1+ tumor cells. PD-L1 positivity on lymphocytes and/or tumor cells was observed for more than half of the patients, with significant differences according to the histological subtype (p<0.001). Patients with a sarcomatoid histology showed the most PD-1 expression. TIM-3 was expressed in tumor cells, stromal lymphocytes and plasma cells, less often in pretreated samples compared to untreated samples. All samples were negative for LAG-3. After multivariate analysis stromal CD45RO expression was found to be an independent negative predictive factor for response to chemotherapy (p=0.017) and expression of CD4 and TIM-3 in lymphoid aggregates were good prognostic factors (p=0.008; p=0.001).
Conclusion:
Our data reveal the diversity of immune cells present in MPM and point to TIM-3 as a new target in mesothelioma. Administering chemotherapy before or together with PD-1/PD-L1/TIM-3 blocking agents may not be the best combination sequence and further research on the predictive value of CD45RO in the stroma might guide patient selection for chemotherapy.
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P1.03 - Poster Session with Presenters Present (ID 455)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Radiology/Staging/Screening
- Presentations: 1
- Moderators:
- Coordinates: 12/05/2016, 14:30 - 15:45, Hall B (Poster Area)
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P1.03-078 - Size Matters...but Don't Underestimate the Power of Morphology (ID 4181)
14:30 - 15:45 | Author(s): P. Pauwels
- Abstract
Background:
The detection of solitary pulmonary nodules has increased due to the widespread use of Computed Tomography (CT) and will increase even more in the future when lung cancer screening will be embedded in daily practice. In addition to the clinical information, size is one of the most important parameters to assess the likelihood of malignancy. Although there is a considerable overlap in imaging characteristics of benign and malignant solitary pulmonary nodules, the power of morphology –even in small nodules- should not be underestimated. The aim of this pictorial essay is to give an overview of the wide range of morphologic characteristics and to address the available evidence on sensitivity and specificity of these characteristics.
Methods:
Cases presented were collected during the Multidisciplinary Thoracic Oncology Tumor Board between January 2014 and May 2016. All malignant cases have histopathologic proof, whereas benign lesions were included when the benign nature was suggested after follow-up, negative PET-scan and/or multidisciplinary consensus.
Results:
With regard to margin characteristics, spiculation is highly suggestive of a malignant nature. It is the only feature that is incorporated as ‘morphologic’ variable in most risk prediction models. Other features however may also be strong indicators of malignancy. Lobulation, halo sign, pleural indentation, vascular convergence sign and pitfall sign are frequently encountered in malignant nodules. The nodule-bronchus relationship can give additional information regarding the nature of the nodule, with signs such as air bronchogram, bubble like lucencies and bronchus cutoff sign being indicative of a malignant nature. In cavitated nodules, a very thin wall might indicate a benign cause, whereas a very thick wall is more common in malignant nodules. Calcification is typically seen in benign nodules, but depending on the calcification pattern a malignant etiology cannot be excluded. The presence of fat is a relative reliable sign of benignity. Thin-section CT will enable detection of subtle findings. Nodules rarely present with only one characteristic and combination of findings can definitely increase the likelihood of a correct diagnosis.
Conclusion:
The management of solitary pulmonary nodules involves both clinical and imaging assessment. Although a great overlap exists in morphologic features of benign and malignant nodules, thorough knowledge and recognition of subtle morphologic findings will aid in early detection of nodules with a high likelihood of malignancy and will avoid unnecessary follow-up and delay in diagnosis and treatment.
