E.D. Kwon

B7-H1(PD-L1) confers chemoresistance through ERK and p38 MAPK pathway in tumor cells

Development of resistance to chemotherapy and immunotherapy is a major obstacle in extending the survival of patients with cancer. Although several molecular mechanisms have been identified that can contribute to chemoresistance, the role of immune checkpoint molecules in tumor chemoresistance remains underestimated. It has been recently observed that overexpression of B7-H1(PD-L1) confers chemoresistance in human cancers, however the underlying mechanisms are unclear. Here we show that the development of chemoresistance depends on the increased activation of ERK pathway in tumor cells overexpressing B7-H1. Conversely, B7-H1 deficiency renders tumor cells susceptible to chemotherapy in a cell-context dependent manner through activation of the p38 MAPK pathway. B7-H1 in tumor cells associates with the catalytic subunit of a DNA-dependent serine / threonine protein kinase (DNA-PKcs). DNA-PKcs is required for the activation of ERK or p38 MAPK in tumors expressing B7-H1, but not in B7-H1 negative or B7-H1 deficient tumors. Ligation of B7-H1 by anti-B7-H1 monoclonal antibody (H1A) increased the sensitivity of human triple negative breast tumor cells to cisplatin therapy in vivo. Our results suggest that B7-H1(PD-L1) expression in cancer cells modifies their chemosensitivity towards certain drugs and targeting B7-H1 intracellular signaling pathway is a new way to overcome cancer chemoresistance.

PS01.12: C11-Choline Positron Emission Tomography and the Detection of Primary Lung Cancers: Topic: Medical Oncology

diagnoses in the first 162 T0 scans (3%), 4 of 5 were AAs. Of these cancers, 60% were stage I vs 63% in NLST. Conclusion: UIHSP demonstrated a right-shift in LungRADS scores and a higher LC rate which raises the question: Do CMS guidelines properly align with LC risk in minority populations such as UIHSP? Moreover, UIHSP had a higher LungRADS 3 (15.4% vs 1.2%) and 4 (15.4% vs 4.6%). LC diagnostic rates were also 3x NLST (3% vs 1%). These are consistent with the known higher LC incidence and mortality among AA men compared to C men (incidence 87.3 vs. 72.5; mortality 70.1 vs. 57.8 per 100,000).

Poster SessionsPS01.12: C11-Choline Positron Emission Tomography and the Detection of Primary Lung Cancers: Topic: Medical Oncology

diagnoses in the first 162 T0 scans (3%), 4 of 5 were AAs. Of these cancers, 60% were stage I vs 63% in NLST. Conclusion: UIHSP demonstrated a right-shift in LungRADS scores and a higher LC rate which raises the question: Do CMS guidelines properly align with LC risk in minority populations such as UIHSP? Moreover, UIHSP had a higher LungRADS 3 (15.4% vs 1.2%) and 4 (15.4% vs 4.6%). LC diagnostic rates were also 3x NLST (3% vs 1%). These are consistent with the known higher LC incidence and mortality among AA men compared to C men (incidence 87.3 vs. 72.5; mortality 70.1 vs. 57.8 per 100,000).

PS01.12: C11-Choline Positron Emission Tomography and the Detection of Primary Lung Cancers

diagnoses in the first 162 T0 scans (3%), 4 of 5 were AAs. Of these cancers, 60% were stage I vs 63% in NLST. Conclusion: UIHSP demonstrated a right-shift in LungRADS scores and a higher LC rate which raises the question: Do CMS guidelines properly align with LC risk in minority populations such as UIHSP? Moreover, UIHSP had a higher LungRADS 3 (15.4% vs 1.2%) and 4 (15.4% vs 4.6%). LC diagnostic rates were also 3x NLST (3% vs 1%). These are consistent with the known higher LC incidence and mortality among AA men compared to C men (incidence 87.3 vs. 72.5; mortality 70.1 vs. 57.8 per 100,000).