Abstract 1323: Both programmed cell death protein 1 and programmed death-ligand 1 molecules can be expressed on the cell surface of small-cell lung cancer

Abstract

Background: Programmed cell death protein-1 (PD-1) and programmed death ligand-1 (PD-L1) play a major role in suppressing the immune system by forming the PD-1/PD-L1 complex, which transmits an inhibitory signal to reduce T-cell activity. PD-L1 is often expressed in various malignant tumors. On the other hand, PD-1 is generally observed in activated lymphocytes and myeloid-derived dendritic cells. Of the malignant cells, only Jurkat cells (under special conditions) and angioimmunoblastic T-cell lymphoma tissue cells express PD-1 on their surface. Purpose: To clarify whether PD-1/PD-L1 complex participates in the immunotolerance on small-cell lung cancer (SCLC) cells. Materials and methods: We examined the expression levels of PD-1 and PD-L1 on the cell surface of SCLC cell lines using flowcytometry and reverse transcription polymerase chain reaction. Subsequently, the soluble PD-L1 (sPD-L1) concentration was measured using enzyme-linked immunosorbent assay, and the cell growth inhibitory effect of IFN-γ was determined by direct cell counting using a hemocytometer and Trypan blue staining. Results: Among the four SCLC cell lines examined, only SBC-3 cells expressed both PD-1 and PD-L1. The sPD-L1 concentrations in culture medium gradually increased according to cell growth. Although IFN-γ alone inhibited the growth of SBC-3 cells, PD-L1 expression on the cell surface was not induced by IFN-γ. Conclusions: We demonstrated that both PD-1 and PD-L1 molecules are co-expressed on the surface of SCLC cells. Although the biological implications of this remain unclear, we speculate that PD-1 and its ligand on the SCLC cells may participate in the growth inhibition of tumor cells as is reported in cytotoxic T cells. Citation Format: Hiromichi Yamane, Hideko Isozaki, Nobuaki Ochi, Kenichiro Kudo, Yoshihiro Honda, Tomoko Yamagishi, Toshio Kubo, Katsuyuki Kiura, Nagio Takigawa. Both programmed cell death protein 1 and programmed death-ligand 1 molecules can be expressed on the cell surface of small-cell lung cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1323. doi:10.1158/1538-7445.AM2015-1323

Targeting DNA Damage Response Promotes Antitumor Immunity through STING-Mediated T-cell Activation in Small Cell Lung Cancer

“…High mutational burden has been reported as a potential predictor of response to immunotherapy ( 8 ). However, despite having one of the highest mutational burdens, small cell lung cancer (SCLC) is often accompanied by relatively high immunosuppression with low levels of T-cell infi ltration and reduced antigen presentation (9)(10)(11). Consistent with this, clinical trials investigating PD-1 or PD-L1 blockade in patients with SCLC have shown low overall response rates ( 12,13 ).…”

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“…Albeit rare, there are also reports on the promising efficacy of PD-L1 and PD-1 antibodies in SCLC patients, both PD-L1-positive and PD-L1-unselected populations [ 14 – 15 ]. Both PD-1 and PD-L1 are expressed on the surface of SCLC cells, though the biological implications and the exact functions of PD-1 and PD-L1 in SCLC remain unclear [ 16 ].…”

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“…3 PD-1, PD-L1, and PD-L2 are also overexpressed in various types of tumors, 2 including non-small cell lung cancer (NSCLC). 4,5 This adoption of the PD-1, so-called immune checkpoint, pathway by some tumors enables them to evade surveillance by the immune system, allowing them to grow unchecked. 6,7 The association between tumor PD-L1 expression and prognosis in patients with solid tumors, including NSCLC, has been explored, with findings suggesting a generally negative prognostic effect.…”