TY - JOUR
T1 - Female Gender Predicts Augmented Immune Infiltration in Lung Adenocarcinoma
AU - Behrens, Carmen
AU - Rocha, Pedro
AU - Parra, Edwin R.
AU - Feng, Lei
AU - Rodriguez-Canales, Jaime
AU - Solis, Luisa M.
AU - Mino, Barbara
AU - Zhang, Jianjun
AU - Gibbons, Don L.
AU - Sepesi, Boris
AU - Rice, David
AU - Heymach, John V.
AU - Moran, Cesar
AU - Creighton, Chad J.
AU - Lee, J. Jack
AU - Kadara, Humam
AU - Wistuba, Ignacio I.
N1 - Funding Information:
This study was supported in part by a Cancer Prevention Research Institute of Texas Multi-Investigator Research Award (RP160668), The University of Texas Lung Specialized Programs of Research Excellence grant (P50CA70907 to I.I.W.), also by MD Anderson's Institutional Tissue Bank Award through the Cancer Center Support Grant (P30CA016672) from the National Cancer Institute, National Institutes of Health/National Cancer Institute grant CA125123, and by Sociedad Espa?ola de Oncolog?a M?dica. The authors thanks to the Scientific Publications, Research Medical Library at MD Anderson Cancer Center in Houston.
Funding Information:
This study was supported in part by a Cancer Prevention Research Institute of Texas Multi-Investigator Research Award ( RP160668 ), The University of Texas Lung Specialized Programs of Research Excellence grant ( P50CA70907 to I.I.W.), also by MD Anderson’s Institutional Tissue Bank Award through the Cancer Center Support Grant ( P30CA016672 ) from the National Cancer Institute , National Institutes of Health /National Cancer Institute grant CA125123 , and by Sociedad Española de Oncología Médica . The authors thanks to the Scientific Publications, Research Medical Library at MD Anderson Cancer Center in Houston.
Publisher Copyright:
© 2020 Elsevier Inc.
PY - 2021/5
Y1 - 2021/5
N2 - Introduction: Immune infiltration in lung adenocarcinomas (LUADs) has been associated with response to immune checkpoint inhibitors. Clinical features underlying differential responses of patients with LUADs to immunotherapy are not well understood. Here, we analyzed the association between LUAD immune infiltration and clinicopathologic variables. Materials and Methods: Intratumoral CD3, CD8, and CD68 cell densities (tumor-associated immune cells [TAICs]) were immunohistochemically assessed in 146 surgically resected LUADs. LUADs were classified into 2 groups, low and high TAICs, based on the median values of cell densities for CD3, CD8, and CD68. Somatic mutation burden and driver gene mutation status were analyzed in a subset of the cases (n = 92). We statistically analyzed the association between the TAIC groups and various clinicopathologic and molecular variables by using the χ2/Fisher and Wilcoxon sum tests and multivariable logistic regression models. Results: Patient gender, tumor size, and STK11 mutations were significantly associated with TAIC levels in LUAD. Female patients exhibited significantly elevated TAIC levels (P = .005) compared with male patients. Tumor size was inversely associated with TAIC levels (P = .012). STK11 mutated tumors were associated with lower TAICs (P = .008). Higher TAICs were consistently observed in female patients with LUADs after adjusting for stage, tumor size, and age. Multivariable regression models confirmed female gender as an independent variable associated with TAIC levels in LUAD (P = .0141). Conclusion: Immune infiltration in LUADs was significantly higher in female patients, warranting further exploration into the association between this clinical variable and immunotherapeutic response in LUAD.
AB - Introduction: Immune infiltration in lung adenocarcinomas (LUADs) has been associated with response to immune checkpoint inhibitors. Clinical features underlying differential responses of patients with LUADs to immunotherapy are not well understood. Here, we analyzed the association between LUAD immune infiltration and clinicopathologic variables. Materials and Methods: Intratumoral CD3, CD8, and CD68 cell densities (tumor-associated immune cells [TAICs]) were immunohistochemically assessed in 146 surgically resected LUADs. LUADs were classified into 2 groups, low and high TAICs, based on the median values of cell densities for CD3, CD8, and CD68. Somatic mutation burden and driver gene mutation status were analyzed in a subset of the cases (n = 92). We statistically analyzed the association between the TAIC groups and various clinicopathologic and molecular variables by using the χ2/Fisher and Wilcoxon sum tests and multivariable logistic regression models. Results: Patient gender, tumor size, and STK11 mutations were significantly associated with TAIC levels in LUAD. Female patients exhibited significantly elevated TAIC levels (P = .005) compared with male patients. Tumor size was inversely associated with TAIC levels (P = .012). STK11 mutated tumors were associated with lower TAICs (P = .008). Higher TAICs were consistently observed in female patients with LUADs after adjusting for stage, tumor size, and age. Multivariable regression models confirmed female gender as an independent variable associated with TAIC levels in LUAD (P = .0141). Conclusion: Immune infiltration in LUADs was significantly higher in female patients, warranting further exploration into the association between this clinical variable and immunotherapeutic response in LUAD.
KW - CD3
KW - CD68
KW - CD8
KW - Gender disparity
KW - Tumor immune infiltration
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U2 - 10.1016/j.cllc.2020.06.003
DO - 10.1016/j.cllc.2020.06.003
M3 - Article
C2 - 32763065
AN - SCOPUS:85088987655
SN - 1525-7304
VL - 22
SP - e415-e424
JO - Clinical Lung Cancer
JF - Clinical Lung Cancer
IS - 3
ER -