Accumulation of small peritoneal macrophages and dendritic cells in a concomitant immunity model associated with prolonged survival.
This study investigated the contribution of peritoneal macrophages to tumor control using a DBA/2-SL2 murine model of concomitant tumor immunity.
Female DBA/2 mice were subjected to a concomitant tumor model in which SL2 lymphoma cells were injected subcutaneously (SC) to establish a primary tumor, followed by intraperitoneal (IP) SL2 challenge to induce secondary tumors. Peritoneal immune cells were analyzed by flow cytometry 4 days after IP challenge. Absolute cell numbers were calculated from total viable cell recovery. To assess functional antitumor activity, CD11b+F4/80+ peritoneal macrophages were isolated by magnetic separation and adoptively transferred into naïve mice together with SL2 cells. In additional experiments, mice received repeated IP injections of SL2 cells. Non-parametric statistical tests were used for data analysis.
Prolonged survival in mice with secondary IP SL2 tumors was associated with pronounced alterations in peritoneal immune composition. Flow cytometric analysis revealed a marked accumulation of small peritoneal macrophages (SPMs) and dendritic cells (DCs) in mice with secondary IP tumors. Absolute counts of SPMs (CD11bintF4/80int) and DCs (CD11c+) were significantly increased in the secondary IP tumor group, with a positive, not statistically significant, correlation between these population. In contrast, mice with primary IP tumors showed expansion of CD11c-CD11b- F4/80- cells, which may include SL2 tumor cells, reduced numbers of B lymphocytes (CD19+) and large peritoneal macrophages (LPMs) (CD11bhiF4/80hi) and an increased number of CD11blowF4/80int cells. Adoptive transfer of peritoneal macrophages from mice with secondary IP tumors did not prolong survival. Repeated IP administration of SL2 cells was associated with improved survival in mice bearing SC tumors in 3 of 5 mice, compared with 1 of 5 mice in the SC tumor-only group, although this difference did not reach statistical significance.
Prolonged survival of DBA/2 mice with secondary IP SL2 tumors is associated with a distinct peritoneal immune landscape characterized by accumulation of SPMs and DCs. While macrophages alone were insufficient to control tumor growth, repeated IP tumor challenge suggested a trend toward systemic antitumor activity. Collectively, these findings highlight SPMs and DCs as prominent cells associated with survival benefit in this model.
Female DBA/2 mice were subjected to a concomitant tumor model in which SL2 lymphoma cells were injected subcutaneously (SC) to establish a primary tumor, followed by intraperitoneal (IP) SL2 challenge to induce secondary tumors. Peritoneal immune cells were analyzed by flow cytometry 4 days after IP challenge. Absolute cell numbers were calculated from total viable cell recovery. To assess functional antitumor activity, CD11b+F4/80+ peritoneal macrophages were isolated by magnetic separation and adoptively transferred into naïve mice together with SL2 cells. In additional experiments, mice received repeated IP injections of SL2 cells. Non-parametric statistical tests were used for data analysis.
Prolonged survival in mice with secondary IP SL2 tumors was associated with pronounced alterations in peritoneal immune composition. Flow cytometric analysis revealed a marked accumulation of small peritoneal macrophages (SPMs) and dendritic cells (DCs) in mice with secondary IP tumors. Absolute counts of SPMs (CD11bintF4/80int) and DCs (CD11c+) were significantly increased in the secondary IP tumor group, with a positive, not statistically significant, correlation between these population. In contrast, mice with primary IP tumors showed expansion of CD11c-CD11b- F4/80- cells, which may include SL2 tumor cells, reduced numbers of B lymphocytes (CD19+) and large peritoneal macrophages (LPMs) (CD11bhiF4/80hi) and an increased number of CD11blowF4/80int cells. Adoptive transfer of peritoneal macrophages from mice with secondary IP tumors did not prolong survival. Repeated IP administration of SL2 cells was associated with improved survival in mice bearing SC tumors in 3 of 5 mice, compared with 1 of 5 mice in the SC tumor-only group, although this difference did not reach statistical significance.
Prolonged survival of DBA/2 mice with secondary IP SL2 tumors is associated with a distinct peritoneal immune landscape characterized by accumulation of SPMs and DCs. While macrophages alone were insufficient to control tumor growth, repeated IP tumor challenge suggested a trend toward systemic antitumor activity. Collectively, these findings highlight SPMs and DCs as prominent cells associated with survival benefit in this model.
Authors
VanagaitÄ-ŽiÄkienÄ VanagaitÄ-ŽiÄkienÄ, JurÅ”ÄnaitÄ JurÅ”ÄnaitÄ, RadzeviÄius RadzeviÄius, MatuzeviÄienÄ MatuzeviÄienÄ, KaÅ”Äta KaÅ”Äta, EidukeviÄius EidukeviÄius, Characiejus Characiejus
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