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K. Teramoto
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ORAL 18 - Non PD1 Immunotherapy and Angiogenesis (ID 114)
- Event: WCLC 2015
- Type: Oral Session
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:C. Butts, K. Reckamp
- Coordinates: 9/08/2015, 10:45 - 12:15, Four Seasons Ballroom F1+F2
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ORAL18.02 - MUC1-Targeted Dendritic Cell-Based Vaccine Immunotherapy in Patients with Standard Treatments-Refractory Non-Small-Cell Lung Cancer (ID 1193)
10:56 - 11:07 | Author(s): K. Teramoto
- Abstract
- Presentation
Background:
MUC1, a tumor antigen, has been considered to a promising target antigen for cancer immunotherapy because it possesses a potent immunogenicity. It is processed and presented by antigen-presenting cells in a MHC-unrestricted pattern. Dendritic cell-based vaccine immunotherapy can elicit antigen-specific cytotoxic T lymphocytes in tumor-bearing hosts, and activated cytotoxic T lymphocytes are expected to attack cancer cells. In this study, we evaluated the efficacy of MUC1-targeted dendritic cell-based vaccine immunotherapy in patients with standard treatments-refractory advanced non-small-cell lung cancer (NSCLC).
Methods:
The eligibility criteria of this immunotherapy were as follows: histologic or cytologic evidence of NSCLC that had been proven to express MUC1 abundantly; an Eastern Cooperative Oncology Group performance status of 0-2; advanced stage of diseases refractory for other standard cancer treatments. The dendritic cells were prepared from peripheral blood mononuclear cells with cytokines interleukin-4 and granulocyte macrophage colony stimulating factor, were pulsed with MUC1 peptides, and subsequently administered to patients subcutaneously. The vaccinations were repeated bi-weekly, and assessable patients were received at least 6 vaccinations. Tumor response was assessed according to the Response Evaluation Criteria in Solid Tumors. Adverse events were graded according to National Cancer Institute Common Toxicity Criteria.
Results:
From June 2005 and March 2015, 42 patients were treated with dendritic cell-based vaccines, and 29 patients (69.0%) with median age of 61 years (range, 49-84 years) were assessable for tumor responses. The cohort consisted of 18 males and 11 females. As their histological types, 24 patients had adenocarcinomas; 4 patients with squamous cell carcinomas and 1 patient with pleomorphic carcinoma. Among these assessable patients, neither complete response nor partial response was obtained. Seventeen patients had progressive disease as the best response, and 11 patients had stable disease, yielding overall disease control rate of 39.2% (95%CI=20.3-55.6). Median survival time after the vaccines was 10.0 months, and 1-year survival rate was 39.6%. Adverse events related to the vaccines were less frequent. Immunological responses were able to be monitored in five patients, showing that MUC1-specific cytotoxic responses of effector immune cells were achieved in all of those patients, and the population of regulatory T lymphocytes in peripheral blood cells was decreased after the vaccines.
Conclusion:
MUC1-targeted dendritic cell-based vaccine immunotherapy is feasible, and has a potential to control the diseases in patients with refractory NSCLC.
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P2.02 - Poster Session/ Treatment of Localized Disease – NSCLC (ID 210)
- Event: WCLC 2015
- Type: Poster
- Track: Treatment of Localized Disease - NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P2.02-012 - Prediction of Postoperative Pulmonary Function Using CT Volumetry (ID 2515)
09:30 - 09:30 | Author(s): K. Teramoto
- Abstract
Background:
According to some guidelines, prediction of postoperative pulmonary function is important in preoperative assessment for the lung cancer resection. Generally, it used to be calculated the function by Segmental method (S method) or Subsegmental method (SS method). But, the volume of pulmonary (sub) segments varies between individuals. The purpose of this study is to evaluate the efficacy of the prediction of postoperative pulmonary function using CT volumetry.
Methods:
This study included 29 cases who were performed segmentectomy or (bi) lobectomy for primary lung cancer from August 2013 to June 2014. Actual pulmonary function obtained at 6 months postoperation (VC, %VC, FVC, %FVC, FEV1.0, %FEV1.0, DLco’, % DLco’, DLco’/Na’, %DLco’/Na’) was compared with the predicted pulmonary function calculated by S method, SS method and CT volumetry method (CTV method), respectively. CTV method was calculated by Image analysis software (Synapse Vincent; Fuji Film, Japan) which used the preoperative chest CT scan data (mediastinum conditions, 0.5mm thickness).
Results:
The median age of patient was 69 years old, ranging 47 to 83 years old. Seven patients underwent thoracotomy and 22 underwent VATS. Upper lobectomy or upper and middle bilobectomy / upper segmentectomy / middle or lower lobectomy / lower segmentectomy were 12/3/10/4 cases, respectively. These 3 methods were found to have a good correlation with actual pulmonary function. In particular, the CTV method’s function was better correlated with actual VC, %VC, FVC, %FVC, FEV1.0, %FEV1.0(r = 0.909, 0.839, 0.913, 0.849, 0.935, 0.875, respectively). On the other hand, SS method’s function has better correlated with actual DLco’, DLco’/Na’, %DLco’/Na’ (r=0.916, 0.817, 0.789, respectively). The cases of upper lobectomy or upper segmentectomy (U group) were found to overestimate on DLco’/Na’, %DLco’/Na’ (t =4.714, 4.634). The other cases (non-U group) were found to overestimate on FVC, FEV1.0, %FEV1.0 (t=2.446, 3.797, 5.657) .
Conclusion:
CTV method may be better correlated evaluation of the ventilation ability than conventional methods, but the evaluation of the diffusion ability is not. Therefore, in the poor pulmonary function case, it is necessary to selectively use these methods in order to make more accurate predictions. And, you should take care that there is pulmonary function to be overestimated or underestimated by the location.
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P2.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 234)
- Event: WCLC 2015
- Type: Poster
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P2.04-070 - Immunological Characterization of PD-L1-Positive Non-Small Cell Lung Cancer Cells (ID 3077)
09:30 - 09:30 | Author(s): K. Teramoto
- Abstract
Background:
The expression of programmed cell death-ligand 1 (PD-L1) on tumor cells plays an essential role in the suppression of anti-tumor immune responses, thus resulting in tumor progression. However, pathological features of PD-L1-positive cancer cells in non-small cell lung cancer (NSCLC) remain unclear.To clarify the characteristics of NSCLCs that are eligible for the-PD-L1-targeted immunotherapy, we examined the immunological feature of PD-L1-positive tumor cells by immunohistochemical analysis.
Methods:
We stained serial sections of formalin-fixed paraffin-embedded NSCLC tissues from 34 patients who had undergone surgery using antibodies to PD-L1 or major histocompatibility complex (MHC) class I. We also identified tumor infiltrated lymphocytes (TIL) in the section, and analyzed the association between PD-L1 expression and MHC class I expression on tumor cells or TIL around tumor cells.
Results:
The patients with median age of 68 years (range, 49-79 years) consisted of 25 males and 9 females. Histological types included 23 adenocarcinomas, 8 squamous cell carcinomas, 2 adeno-squamous cell carcinomas and 1 pleomorphic carcinoma. PD-L1 and MHC class I were expressed on tumor cells in 28 (82.3%) and 29 (85.3%) of 34 cases, respectively. In 18 of 34 cases (52.9%), MHC class I-positive tumor cells were dominant in the tumor; whereas MHC class I-negative tumor cells were dominant in 16 of 34 cases (47.1%). PD-L1 expression was observed in 14 of 18 (77.7%) NSCLCs that are dominant with MHC class I-positive tumor cells, whereas it was detected in 4 of 16 (25.0%) those mainly containing MHC class I-negative tumor cells. There was a significant association between PD-L1 and MHC class I expressions on NSCLC cells (p=0.0045). We next examined the association between the co-expression of PD-L1 and MHC class I on tumor cells and the number of TIL, and found that the incidence of PD-L1[+ ]MHC class I[+ ]tumor cells was likely to associate with the large number of TIL (r=0.42). The frequency of PD-L1-positive cells in MHC class I-positive tumor cells was also associated with the large number of TIL (r=0.33).
Conclusion:
MHC class I expression on tumor cells may be required for their expression of PD-L1, probably through the cell-to-cell interaction with TIL. Further study is warranted, however, the patient with the co-expression of PD-L1 and MHC class I on larger number of tumor cells is likely to be a suitable candidate for PD-L1-targeted immunotherapy.
