Thibault Vieira1, Martine Antoine2, Cécile Hamard1, Vincent Fallet1, Michael Duruisseaux3, Nathalie Rabbe3, Anita Rodenas4, Jacques Cadranel1, Marie Wislez5. 1. Sorbonne Universités, UPMC Univ. Paris 06, GRC n°04, Theranoscan, F-75252 Paris, France; AP-HP, Hôpital Tenon, service de Pneumologie, F-75970 Paris, France. 2. Sorbonne Universités, UPMC Univ. Paris 06, GRC n°04, Theranoscan, F-75252 Paris, France; AP-HP, Hôpital Tenon, service d'anatomopathologie, F-75970 Paris, France. 3. Sorbonne Universités, UPMC Univ. Paris 06, GRC n°04, Theranoscan, F-75252 Paris, France. 4. AP-HP, Hôpital Tenon, service d'anatomopathologie, F-75970 Paris, France. 5. Sorbonne Universités, UPMC Univ. Paris 06, GRC n°04, Theranoscan, F-75252 Paris, France; AP-HP, Hôpital Tenon, service de Pneumologie, F-75970 Paris, France. Electronic address: marie.wislez@tnn.aphp.fr.
Abstract
OBJECTIVES: Pulmonary sarcomatoid carcinomas (SC) are rare tumors, associated with worse prognosis and resistant to platinum-based regimens. Therapies targeting the PD-1/PD-L1 pathway are an emerging treatment for lung cancer. By characterizing intra-tumoral immune infiltration and evaluating PD-L1 expression, it could be possible to predict the efficacy of these new treatments. MATERIALS AND METHODS: From 1997 to 2013, data from all patients with SC who underwent lung resection was collected. Tumor-immune infiltration and PD-L1 expression were studied by immunochemistry tests, analyzing CD3 (clone SP7), CD4 (clone 1F6), CD8 (clone C8/144b), CD20 (clone L26), CD163 (clone 10D6), MPO (clone 59A5), and PD-L1 (clone 5H1). Results were compared to those of 54 NSCLC. RESULTS: In total, 75 SC were included. Forty (53%) SC expressed PD-L1 vs 11 NSCLC (20%) (p<0.0001). CD3+ tumor-infiltrating lymphocytes and CD163+ tumor-associated macrophages were more important in SC than in NSCLC (median 23% [17-30] of tumoral surface vs 17% [7-27], p=0.011 and 23% [17-30] vs 20% [13-23], p=0.002, respectively). In SC, the presence of Kirsten Ras (KRAS) mutations, blood vessel invasion, and TTF1+ positivity were associated with PDL1 expression. On multivariate analysis, only CD163+ macrophages and blood-vessel invasion were associated with tumoral PD-L1 expression. High levels of tumor-infiltrating lymphocytes (CD3+ or CD4+ and not CD8+) constituted a factor of good prognosis on survival. Interestingly, PD-L1 expression distinguishes subpopulations within tumor-infiltrating lymphocytes (CD3+ or CD4+) with different prognosis CONCLUSIONS: PD-L1 expression was higher in SC than in NSCLC as well as immune-cell infiltration by TCD3 cells and macrophages. This suggests that targeting the PD-1/PD-L1 pathway could represent a new potential therapy.
OBJECTIVES:Pulmonary sarcomatoid carcinomas (SC) are rare tumors, associated with worse prognosis and resistant to platinum-based regimens. Therapies targeting the PD-1/PD-L1 pathway are an emerging treatment for lung cancer. By characterizing intra-tumoral immune infiltration and evaluating PD-L1 expression, it could be possible to predict the efficacy of these new treatments. MATERIALS AND METHODS: From 1997 to 2013, data from all patients with SC who underwent lung resection was collected. Tumor-immune infiltration and PD-L1 expression were studied by immunochemistry tests, analyzing CD3 (clone SP7), CD4 (clone 1F6), CD8 (clone C8/144b), CD20 (clone L26), CD163 (clone 10D6), MPO (clone 59A5), and PD-L1 (clone 5H1). Results were compared to those of 54 NSCLC. RESULTS: In total, 75 SC were included. Forty (53%) SC expressed PD-L1 vs 11 NSCLC (20%) (p<0.0001). CD3+ tumor-infiltrating lymphocytes and CD163+ tumor-associated macrophages were more important in SC than in NSCLC (median 23% [17-30] of tumoral surface vs 17% [7-27], p=0.011 and 23% [17-30] vs 20% [13-23], p=0.002, respectively). In SC, the presence of Kirsten Ras (KRAS) mutations, blood vessel invasion, and TTF1+ positivity were associated with PDL1 expression. On multivariate analysis, only CD163+ macrophages and blood-vessel invasion were associated with tumoral PD-L1 expression. High levels of tumor-infiltrating lymphocytes (CD3+ or CD4+ and not CD8+) constituted a factor of good prognosis on survival. Interestingly, PD-L1 expression distinguishes subpopulations within tumor-infiltrating lymphocytes (CD3+ or CD4+) with different prognosis CONCLUSIONS:PD-L1 expression was higher in SC than in NSCLC as well as immune-cell infiltration by TCD3 cells and macrophages. This suggests that targeting the PD-1/PD-L1 pathway could represent a new potential therapy.
Authors: Matthew Evans; Brendan O'Sullivan; Frances Hughes; Tina Mullis; Matthew Smith; Nicola Trim; Philippe Taniere Journal: Pathol Oncol Res Date: 2018-09-17 Impact factor: 3.201