The Relationship Between Tumor-Infiltrating Lymphocytes, PD-L1 Expression, Driver Mutations and Clinical Outcome Parameters in Non-Small Cell Lung Cancer Adenocarcinoma in Patients with a Limited to no Smoking History

• Published in: Pathology oncology research Vol. 26; no. 2; pp. 1221 - 1228
• Main Authors: Mignon, Sacha, Willard-Gallo, Karen, Van den Eynden, Gert, Salgado, Roberto, Decoster, Lore, Marien, Koen M., Vansteenkiste, Johan F., Teugels, Erik, De Grève, Jacques
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01-04-2020; Springer Nature B.V
• Subjects: Adenocarcinoma; Adenocarcinoma of Lung - genetics; Adenocarcinoma of Lung - immunology; Adult; Aged; Apoptosis; B7-H1 Antigen - biosynthesis; Biomedical and Life Sciences; Biomedicine; Cancer Research; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - immunology; Disease-Free Survival; Female; Humans; Immune response; Immunohistochemistry; Immunology; Infiltration; Lung cancer; Lymphocytes; Lymphocytes, Tumor-Infiltrating - immunology; Male; Medical prognosis; Metastases; Middle Aged; Mutants; Mutation; Non-small cell lung carcinoma; Oncology; Original Article; Pathology; PD-1 protein; PD-L1 protein; Prognosis; Proto-Oncogene Proteins p21(ras) - genetics; Small cell lung carcinoma; Smoking; Stromal cells; Tissue analysis; Tumor cells; Tumor-infiltrating lymphocytes; Tumors; Programmed death-1 (PD-1); Lung adenocarcinoma; Driver mutations; Tumor infiltrating lymphocytes (TIL); Programmed death-ligand 1 (PD-L1)
• ISSN: 1219-4956; 1532-2807
• DOI: 10.1007/s12253-019-00670-9

Tumor infiltrating lymphocytes (TIL), programmed death 1 (PD-1) and programmed death-ligand 1 (PD-L1) expression are important prognostic markers. This study aimed to investigate these markers in lung adenocarcinoma (ADC) biopsies from patients with stage IIIB or IV ADC with little or no smoking history, to investigate their prognostic value and to correlate these results with the presence of driver mutations in the tumors. TIL were retrospectively evaluated on hematoxylin and eosin stained slides from 152 tumor samples. PD-1/PD-L1 expression was retrospectively evaluated with PD-1/PD-L1 immunohistochemistry (IHC) double staining on 74 tumor samples with sufficient residual tissue. PD-L1 expression was analysed on stromal cells of the tumor compartment, the tumor cells and TIL and PD-1 on TIL. Median overall survival (OS) was longer in patients with high stromal TIL infiltration compared to patients with low stromal TIL infiltration (68 weeks vs. 35 weeks respectively;
p
 = 0.003). This was observed most prominently in
KRAS
mutant tumors (95 weeks vs. 12 weeks; p = 0.003). Only PD-L1 expression on tumor stromal cells influenced OS and indicated a worse prognosis (77 weeks vs 25 weeks;
p
 = 0.013). Stromal TIL counts nor PD-1/PD-L1 expression levels were associated with the presence of driver mutations. The results of the current study reinforce the prognostic role of TIL in lung ADC, which is most prominent in
KRAS
mutant cancers. The results of the PD-1/PD-L1 analysis suggest that stromal cells can effectively suppress the anti-tumor immune response via the PD-L1 pathway.