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Ond?ej Palata
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P2.07 - Immunology and Immunotherapy (ID 708)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Immunology and Immunotherapy
- Presentations: 1
- Moderators:
- Coordinates: 10/17/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P2.07-020 - Distinct Immune Status in Patients with Adenocarcinoma and Squamous Cell Carcinoma: Implication for Immunotherapy of NSCLC (ID 8554)
09:30 - 09:30 | Author(s): Ond?ej Palata
- Abstract
Background:
Lung cancer is the leading cause of cancer mortality worldwide therefore understanding the role of immune system in antitumor immunity is of a great interest. Here we compared immune cell infiltration and responses in tumors and non-tumoral lung tissue from 43 adenocarcinomas (AC) and 39 squamous cell carcinomas (SCC) of non-small cell lung cancer patients.
Method:
In this study we compared immune cell populations, T cell responses and secreted cytokines in primary tumors and non-tumoral lung tissue as well as in blood of non-small cell lung cancer (NSCLC) patients undergoing neoadjuvant surgery. Moreover, we compared immune suppressive populations such as CD4[+]CD25[+]Foxp3[+ ]T regulatory cells and myeloid-derived suppressor cells (MDSC).
Result:
Whereas T, B and NK cells infiltration was comparable in AC and SCC, the number of dendritic cells was lower in SCC tumors. CD8[+] T cell and NK cell proliferation, IFN-γ-production from T cells and secretion of proinflammatory cytokines after stimulation in vitro was lower in SCC compared to AC tumors. A higher number of Tregs was detected in tumors and blood of AC patients, whereas a higher number of MDSC was found in SCC patients. The suppressive function of Tregs was comparable between AC and SCC patients, but MDSC in SCC patients displayed a higher suppressive function as shown by inhibition of CD3z expression and IL-2 and IFN-γ production in T cells, Lox-1 plasma concentrations compared to AC patients and age-matched controls.
Conclusion:
Our results suggest that immune system of SCC patients might be subjected to higher immunosuppression than AC patients. Our observations also give rationale to target specifically MDSC in SCC patients and Tregs in AC patients for designing combinatorial immunotherapeutic approaches.
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P3.07 - Immunology and Immunotherapy (ID 723)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Immunology and Immunotherapy
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.07-008 - Development of Immunomonitoring Assays for Dendritic Cell-Based Lung Cancer Immunotherapy (ID 9804)
09:30 - 09:30 | Presenting Author(s): Ond?ej Palata
- Abstract
Background:
Allogeneic cancer cell lines might serve as a universal source of tumor antigens in the development of dendritic cell-based cancer vaccines. We showed that selected antigenic profile of lung cancer cell lines overlaps with antigenic profile of primary non/small cell lung cancer (NSCLC) tumors. However, it is unclear if T cells responses to all of these antigens can be detected in blood of NSCLC patients.
Method:
Peripheral blood mononuclear cells (PBMCs) of NSCL patients were stimulated and re-stimulated by commercially available mixes of antigenic peptides derived from these antigens over the course of 10 days. Tumor antigen-specific CD8[+] and CD4[+] T cells were characterized by IFN-γ production, granzyme B, perforin, an d CD137 or CD154 expression by flow cytometry. In addition, the expression of inhibitory molecules TIM3, CTLA-4, PD-1 and LAG-3 were evaluated on CD8[+] and CD4[+] T cells from PBMC of NSCLC patients. We further analysed 6 populations of myeloid-derived suppressor cells (MDCS) by a multicolor flow cytometry and their possible functional suppression by qPCR analysis of ARG1 and iNOS expression in PBMC and downregulation of CD3zξ in T cells from patient’s PBMCs compared to T cells from PBMCs of healthy donors.
Result:
We were able to detect tumor antigen-specific IFN-γ, Granzyme B and Perforin producing CD8[+] and CD4[+] T cells as well as expression of inhibitory molecules TIM3, CTLA-4, PD-1 and LAG-3. We were also able to detect populations of MDSCs in blood of NSCLC patients as well as healthy donors.
Conclusion:
This data will allow us to develop a protocol for immunomonitoring studies of the effectivity of dendritic cell-based lung cancer immunotherapy in ongoing phase I lung cancer clinical trial (NCT02470468).
