Universität zu Köln

Schulze, Arik Bernard, Evers, Georg, Goerlich, Dennis, Mohr, Michael, Marra, Alessandro, Hillejan, Ludger, Rehkaemper, Jan, Schmidt, Lars Henning and Heitkoetter, Birdie (2020). Tumor infiltrating T cells influence prognosis in stage I-III non-small cell lung cancer. J. Thorac. Dis., 12 (5). S. 1824 - 1847. SHATIN: AME PUBL CO. ISSN 2077-6624

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Abstract

Background: T cell infiltration in non-small cell lung cancer (NSCLC) is essential for the immunological response to malignant tissue, especially in the era of immune-checkpoint inhibition. To investigate the prognostic impact of CD4(+) T helper cells (T-h), CD8(+) cytotoxic (T-c) and FOXP3(+) regulatory T (T-reg) cells in NSCLC, we performed this analysis. Methods: By counterstaining of CD4, CD8 and FOXP3 we used immunohistochemistry on tissue microarrays (TMA) to evaluate peritumoral T-h cells, T(reg )cells and T-c cells in n=294 NSCLC patients with pTNM stage I-III disease. Results: Strong CD4(+) infiltration was associated with higher tumor stages and lymphonodal spread. However, strong CD4(+) infiltration yielded improved overall survival (OS) (P=0.014) in adenocarcinoma (ADC) and large cell carcinoma (LCC) but not in squamous cell carcinoma (SCC). A CD4/CD8 ratio <1 was associated with high grade NSCLC tumors (P=0.020). High CD8(+) T cell infiltration was an independent prognostic factor for OS (P=0.040) and progression-free survival (PFS) (P=0.012) in the entire study collective. The OS benefit of high CD8(+) infiltration was especially prominent in PD-L1 negative NSCLC (P=0.001) but not in PD-L1 positive tissue (P=0.335). Moreover, positive FOXP3(+) expression in tumor infiltrating lymphocytes was associated with increased OS (P=0.007) and PFS (P=0.014) in SCC but not in ADC and LCC (all P>0.05). Here, prognostic effects were prominent in PD-L1 positive SCC (P=0.023) but not in PD-L1 negative SCC (P=0.236). Conclusions: High proportion of CD8(+) T-c cells correlated with improved prognostic outcome in stage I-III NSCLC. T-h cells and T-reg cells have implications on outcome with respect to tumor histology and biology.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Schulze, Arik Bernard UNSPECIFIED UNSPECIFIED UNSPECIFIED Evers, Georg UNSPECIFIED UNSPECIFIED UNSPECIFIED Goerlich, Dennis UNSPECIFIED UNSPECIFIED UNSPECIFIED Mohr, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Marra, Alessandro UNSPECIFIED UNSPECIFIED UNSPECIFIED Hillejan, Ludger UNSPECIFIED UNSPECIFIED UNSPECIFIED Rehkaemper, Jan UNSPECIFIED UNSPECIFIED UNSPECIFIED Schmidt, Lars Henning UNSPECIFIED UNSPECIFIED UNSPECIFIED Heitkoetter, Birdie UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-335049
DOI:	10.21037/jtd-19-3414a
Journal or Publication Title:	J. Thorac. Dis.
Volume:	12
Number:	5
Page Range:	S. 1824 - 1847
Date:	2020
Publisher:	AME PUBL CO
Place of Publication:	SHATIN
ISSN:	2077-6624
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language EPITHELIAL-MESENCHYMAL TRANSITION; FOXP3 EXPRESSION; MICROENVIRONMENT; TISSUE; IMMUNOTHERAPY; CD4(+); NSCLC Multiple languages Respiratory System Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/33504