Long-term survival for patients with non-small-cell lung cancer with intratumoral lymphoid structures.
OBJECTIVE
It has been established that the immune system plays an important role in tumor rejection. There is also compelling evidence that immune responses can develop independently of secondary lymphoid organs in tertiary lymphoid structures. We studied the presence and the correlation of tertiary lymphoid structures with clinical outcome in non-small-cell lung cancer (NSCLC), as the prognostic value of these structures in patients with cancer had not yet been established.


METHODS
This retrospective study was performed by immunohistochemistry on paraffin-embedded tissue specimens from 74 patients with early-stage NSCLC.


RESULTS
Tertiary lymphoid structures were detected in some tumors but not in nontumoral lungs. Thus we called these structures tumor-induced bronchus-associated lymphoid tissue (Ti-BALT). As in lymph nodes, Ti-BALTs were composed of mature dendritic cell (DC)/T-cell clusters adjacent to B-cell follicles and had features of an ongoing immune response. Because the quantitative counting of Ti-BALT was difficult to achieve, we used mature DCs that homed exclusively in Ti-BALT as a specific marker of these structures. Univariate analysis showed that the density of mature DCs was highly associated with a favorable clinical outcome (overall, disease-specific, and disease-free survival), suggesting that Ti-BALT may participate in antitumoral immunity. The density of tumor-infiltrating lymphocytes, in particular, CD4(+) and T-bet(+) Th1 T cells, was profoundly decreased in tumors weakly infiltrated by mature DCs.


CONCLUSIONS
The density of mature DCs was found to be a better predictor of clinical outcome than the other parameters tested. The number of tumor-infiltrating mature DCs may identify patients with early-stage NSCLC who have a high risk of relapse.
Dieu-Nosjean
Marie-Caroline
MC
Laboratoire Microenvironnement, Immunitaire et Tumeurs, Institut National de la Santé et de la Recherche Médicale (INSERM) U872, Centre de Recherche des Cordeliers, Paris cedex 06, France. mc.dieu-nosjean@crc.jussieu.fr
Antoine
Martine
M
Danel
Claire
C
Heudes
Didier
D
Wislez
Marie
M
Poulot
Virginie
V
Rabbe
Nathalie
N
Laurans
Ludivine
L
Tartour
Eric
E
de Chaisemartin
Luc
L
Lebecque
Serge
S
Fridman
Wolf-Herman
WH
Cadranel
Jacques
J
D000328:Adult; D000368:Aged; D001706:Biopsy; D018791:CD4 Lymphocyte Count; D002289:Carcinoma, Non-Small-Cell Lung / Q000276:immunology / Q000401:mortality* / Q000473:pathology*; D002452:Cell Count; D002828:Choristoma / Q000276:immunology / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000276:immunology / Q000401:mortality* / Q000473:pathology*; D008198:Lymph Nodes; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011230:Precancerous Conditions / Q000276:immunology / Q000473:pathology; D011379:Prognosis; D012189:Retrospective Studies; D015996:Survival Rate; D016176:T-Lymphocyte Subsets / Q000473:pathology