Abstract 1724: Pancancer evaluation of tumor infiltrating lymphocytes (TILs) and PD-L1 in SHIVA-01 trial patients with different biopsy sites and histological types
Authors: Beaino Zakhia El , Dupain Célia , Marret Grégoire , Paoletti Xavier , Fuhrmann Laëtitia , Martinat Charlotte , Bièche Ivan , Tourneau Christophe Le , Kamal Maud , Vincent-Salomon Anne 
Published: June 2022

Abstract
Background: Immunologic characterization of tumors and their microenvironments had been proposed based on the combination of PD-L1 expression and the presence of tumor-infiltrating lymphocytes (TILs). This study aims to investigate in metastatic samples from patients with cancer, the distribution of TILs and expression of PD-L1 using Combined Positive Score (CPS), Tumor Proportion Score (TPS), as well as TILs. These variables were further evaluated in paired primary and metastatic samples and correlated with clinical outcome.
Patients and methods: 550 pan-cancer patients of SHIVA01 trial (NCT01771458) with available contributive FFPE sample from a metastatic biopsy and 111 paired primary and metastatic samples were evaluated for TILs. The 550 metastatic specimens were biopsies from different anatomical sites subdivided into 7 groups: liver biopsies (n=179; 33%), visceral organ biopsies (n=92; 17%), lung biopsies (n=89; 16%), lymph node biopsies (n= 88; 16%), cutaneous biopsies (n=53; 10%), soft tissue biopsies (n=48; 9%) and brain biopsy (n=1; 0.2%). PD-L1 expression was assessed by Immunohistochemistry using the 22C3 antibody clone (Merck & Co) and quantified using two scores: CPS and TPS, in 494 metastatic tumors and in 77 paired primary and metastatic tumors patients with contributive immunohistochemistry. The correlations of TILs and PD-L1 expression with clinical outcomes are ongoing.
Results: In metastatic samples, we found no difference in TILs distribution according to histological subtype, primary system or biopsy site with a median of 10% [range: 0%-70%]. A significant decrease in the median percentage of TILs was found in metastases in comparison to their paired primary lesions (20% [5%-60%] versus 10% [0%-40%], p&lt;0.0001). PD-L1 expression was homogenous in all metastatic tumors independently of primary system or biopsy site (median TPS = 2% ; CPS = 0 n=218, CPS≥1 n=265 ; p=0.056). There was a strong association between TPS count and histological subtypes (p=0.015) that was not observed with CPS (p=0.23). In paired primary/metastatic samples, we did not observe any changes in the CPS and TPS scores (p&gt;0.3 for both).
Conclusion: We show that metastatic sites are less infiltrated with lymphocytes as compared to their paired primary lesions independently of the initial primary tumor site, histological type or biopsy site. PD-L1 expression was similar in paired primary and metastatic samples.
Citation Format: Zakhia El Beaino, Célia Dupain, Grégoire Marret, Xavier Paoletti, Laëtitia Fuhrmann, Charlotte Martinat, Ivan Bièche, Christophe Le Tourneau, Maud Kamal, Anne Vincent-Salomon. Pancancer evaluation of tumor infiltrating lymphocytes (TILs) and PD-L1 in SHIVA-01 trial patients with different biopsy sites and histological types [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1724.