TY - JOUR
T1 - High density and proximity of CD8+ T cells to tumor cells are correlated with better response to nivolumab treatment in metastatic pleural mesothelioma
AU - Yin, Yuting
AU - Sakakibara, Rie
AU - Honda, Takayuki
AU - Kirimura, Susumu
AU - Daroonpan, Pissacha
AU - Kobayashi, Masashi
AU - Ando, Kohei
AU - Ujiie, Hideki
AU - Kato, Tatsuya
AU - Kaga, Kichizo
AU - Mitsumura, Takahiro
AU - Nakano, Ryoji
AU - Sakashita, Hiroyuki
AU - Matsuge, Shinichi
AU - Ishibashi, Hironori
AU - Akashi, Takumi
AU - Hida, Yasuhiro
AU - Morohoshi, Takao
AU - Azuma, Miyuki
AU - Okubo, Kenichi
AU - Miyazaki, Yasunari
N1 - Publisher Copyright:
© 2023 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.
PY - 2023/7
Y1 - 2023/7
N2 - Background: The efficacy of immune checkpoint inhibitors (ICIs) in pleural mesothelioma has recently been established. The response to ICIs can be predicted by quantitative analysis of cells and their spatial distribution in the tumor microenvironment (TME). However, the detailed composition of the TME in pleural mesothelioma has not been reported. We evaluated the association between the TME and response to ICIs in this cancer. Methods: A retrospective analysis of 22 pleural mesothelioma patients treated with nivolumab in different centers was performed using surgical specimens. Four patients had a partial response to nivolumab (response group) and 18 patients had stable or progressive disease (nonresponse group). The number of CD4, CD8, FoxP3, CK, and PD-L1 positive cells, cell density, and cell-to-cell distance were analyzed by multiplex immunofluorescence. Results: PD-L1 expression did not differ significantly between the response and nonresponse groups. The density of total T cells and of CD8+ T cells was significantly higher in the response than in the nonresponse group. CD8+ T cells were more clustered and located closer to tumor cells, whereas regulatory T cells were located further from tumor cells in the response than in the nonresponse group. Conclusions: High density and spatial proximity of CD8+ T cells to tumor cells were associated with better response to nivolumab, whereas the proximity of regulatory T cells to tumor cells was associated with worse response, suggesting that the distinct landscape of the TME could be a potential predictor of ICI efficacy in pleural mesothelioma.
AB - Background: The efficacy of immune checkpoint inhibitors (ICIs) in pleural mesothelioma has recently been established. The response to ICIs can be predicted by quantitative analysis of cells and their spatial distribution in the tumor microenvironment (TME). However, the detailed composition of the TME in pleural mesothelioma has not been reported. We evaluated the association between the TME and response to ICIs in this cancer. Methods: A retrospective analysis of 22 pleural mesothelioma patients treated with nivolumab in different centers was performed using surgical specimens. Four patients had a partial response to nivolumab (response group) and 18 patients had stable or progressive disease (nonresponse group). The number of CD4, CD8, FoxP3, CK, and PD-L1 positive cells, cell density, and cell-to-cell distance were analyzed by multiplex immunofluorescence. Results: PD-L1 expression did not differ significantly between the response and nonresponse groups. The density of total T cells and of CD8+ T cells was significantly higher in the response than in the nonresponse group. CD8+ T cells were more clustered and located closer to tumor cells, whereas regulatory T cells were located further from tumor cells in the response than in the nonresponse group. Conclusions: High density and spatial proximity of CD8+ T cells to tumor cells were associated with better response to nivolumab, whereas the proximity of regulatory T cells to tumor cells was associated with worse response, suggesting that the distinct landscape of the TME could be a potential predictor of ICI efficacy in pleural mesothelioma.
KW - immune checkpoint inhibitor (ICI)
KW - multiplex immunofluorescence (mIF)
KW - nivolumab
KW - pleural mesothelioma
KW - tumor microenvironment (TME)
UR - http://www.scopus.com/inward/record.url?scp=85161353322&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85161353322&partnerID=8YFLogxK
U2 - 10.1111/1759-7714.14981
DO - 10.1111/1759-7714.14981
M3 - Article
C2 - 37253418
AN - SCOPUS:85161353322
SN - 1759-7706
VL - 14
SP - 1991
EP - 2000
JO - Thoracic Cancer
JF - Thoracic Cancer
IS - 20
ER -