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PHILADELPHIA—New research suggests the prognostic value of tumor-associated macrophages (TAMs) is disease-specific as well as treatment-specific.
Investigators set out to determine if TAMs have a negative prognostic impact in diffuse large B-cell lymphoma (DLBCL), as previous studies produced conflicting results.
The team found that higher TAM levels are associated with worse survival in DLBCL, but only in patients who do not receive rituximab. The drug can overcome the poor prognosis TAMs confer in DLBCL.
Eri Matsuki, MD, PhD, of Memorial Sloan-Kettering Cancer Center in New York, New York, and her colleagues presented these findings in a poster at the AACR Annual Meeting 2015 (abstract 2371*).
To ascertain the role of TAMs in DLBCL, the investigators analyzed specimens from 103 DLBCL patients, 61 of whom received rituximab, 33 who did not, and 9 whose rituximab status was unknown. The team first looked at the expression of CD163 as a marker of TAMs.
“CD163 is more specific to M2-type macrophages, which have pro-tumor effects, compared to a more pan-macrophage marker which is widely used—CD68,” Dr Matsuki noted.
She and her colleagues found that a high level of CD163-positive cells (more than 150) was significantly associated with advanced-stage disease (P=0.016), non-GCB DLBCL (P=0.0071), and higher expression of c-Myc (P=0.0022).
“Our interpretation of that at this point is that, the more aggressive the tumor, the more likely that it would induce macrophages into the tissue,” Dr Matsuki said.
The investigators then assessed the impact of rituximab use. Among patients who didn’t receive rituximab, having a high level of CD163-positive cells (more than 150) was associated with inferior overall survival (OS, P=0.022). However, if patients did receive rituximab, there was no significant difference in OS.
Dr Matsuki said this supports previous studies showing that the prognostic effect of TAMs diminishes with rituximab use, as well as the in vitro finding that M2 macrophages exhibit increased phagocytosis of rituximab-opsonized tumor cells.
“So overall, what we’re seeing is that . . . the negative influence of TAMs can be overcome with rituximab use,” she summarized.
Dr Matsuki and her colleagues also looked at the patients’ lymphocyte-to-monocyte-ratio (LMR) because TAMs partly arise from peripheral blood monocytes.
The team found that having an LMR higher than 2.77 was significantly associated with superior OS (P=0.03) in patients who did not receive rituximab. And there was a trend toward improved OS with a higher LMR in patients who did receive the drug (P=0.07).
The investigators believe the differences they observed in the prognostic value of CD163 and LMR could be explained by the fact that TAMs are derived from both circulating monocytes and resident macrophages.
Dr Matsuki said this research has improved her group’s understanding of DLBCL, but they are still working to identify additional biomarkers associated with prognosis in this disease. 
*Information in the abstract differs from that presented at the meeting.
pseudopodia to engulf particles
PHILADELPHIA—New research suggests the prognostic value of tumor-associated macrophages (TAMs) is disease-specific as well as treatment-specific.
Investigators set out to determine if TAMs have a negative prognostic impact in diffuse large B-cell lymphoma (DLBCL), as previous studies produced conflicting results.
The team found that higher TAM levels are associated with worse survival in DLBCL, but only in patients who do not receive rituximab. The drug can overcome the poor prognosis TAMs confer in DLBCL.
Eri Matsuki, MD, PhD, of Memorial Sloan-Kettering Cancer Center in New York, New York, and her colleagues presented these findings in a poster at the AACR Annual Meeting 2015 (abstract 2371*).
To ascertain the role of TAMs in DLBCL, the investigators analyzed specimens from 103 DLBCL patients, 61 of whom received rituximab, 33 who did not, and 9 whose rituximab status was unknown. The team first looked at the expression of CD163 as a marker of TAMs.
“CD163 is more specific to M2-type macrophages, which have pro-tumor effects, compared to a more pan-macrophage marker which is widely used—CD68,” Dr Matsuki noted.
She and her colleagues found that a high level of CD163-positive cells (more than 150) was significantly associated with advanced-stage disease (P=0.016), non-GCB DLBCL (P=0.0071), and higher expression of c-Myc (P=0.0022).
“Our interpretation of that at this point is that, the more aggressive the tumor, the more likely that it would induce macrophages into the tissue,” Dr Matsuki said.
The investigators then assessed the impact of rituximab use. Among patients who didn’t receive rituximab, having a high level of CD163-positive cells (more than 150) was associated with inferior overall survival (OS, P=0.022). However, if patients did receive rituximab, there was no significant difference in OS.
Dr Matsuki said this supports previous studies showing that the prognostic effect of TAMs diminishes with rituximab use, as well as the in vitro finding that M2 macrophages exhibit increased phagocytosis of rituximab-opsonized tumor cells.
“So overall, what we’re seeing is that . . . the negative influence of TAMs can be overcome with rituximab use,” she summarized.
Dr Matsuki and her colleagues also looked at the patients’ lymphocyte-to-monocyte-ratio (LMR) because TAMs partly arise from peripheral blood monocytes.
The team found that having an LMR higher than 2.77 was significantly associated with superior OS (P=0.03) in patients who did not receive rituximab. And there was a trend toward improved OS with a higher LMR in patients who did receive the drug (P=0.07).
The investigators believe the differences they observed in the prognostic value of CD163 and LMR could be explained by the fact that TAMs are derived from both circulating monocytes and resident macrophages.
Dr Matsuki said this research has improved her group’s understanding of DLBCL, but they are still working to identify additional biomarkers associated with prognosis in this disease.
*Information in the abstract differs from that presented at the meeting.
pseudopodia to engulf particles
PHILADELPHIA—New research suggests the prognostic value of tumor-associated macrophages (TAMs) is disease-specific as well as treatment-specific.
Investigators set out to determine if TAMs have a negative prognostic impact in diffuse large B-cell lymphoma (DLBCL), as previous studies produced conflicting results.
The team found that higher TAM levels are associated with worse survival in DLBCL, but only in patients who do not receive rituximab. The drug can overcome the poor prognosis TAMs confer in DLBCL.
Eri Matsuki, MD, PhD, of Memorial Sloan-Kettering Cancer Center in New York, New York, and her colleagues presented these findings in a poster at the AACR Annual Meeting 2015 (abstract 2371*).
To ascertain the role of TAMs in DLBCL, the investigators analyzed specimens from 103 DLBCL patients, 61 of whom received rituximab, 33 who did not, and 9 whose rituximab status was unknown. The team first looked at the expression of CD163 as a marker of TAMs.
“CD163 is more specific to M2-type macrophages, which have pro-tumor effects, compared to a more pan-macrophage marker which is widely used—CD68,” Dr Matsuki noted.
She and her colleagues found that a high level of CD163-positive cells (more than 150) was significantly associated with advanced-stage disease (P=0.016), non-GCB DLBCL (P=0.0071), and higher expression of c-Myc (P=0.0022).
“Our interpretation of that at this point is that, the more aggressive the tumor, the more likely that it would induce macrophages into the tissue,” Dr Matsuki said.
The investigators then assessed the impact of rituximab use. Among patients who didn’t receive rituximab, having a high level of CD163-positive cells (more than 150) was associated with inferior overall survival (OS, P=0.022). However, if patients did receive rituximab, there was no significant difference in OS.
Dr Matsuki said this supports previous studies showing that the prognostic effect of TAMs diminishes with rituximab use, as well as the in vitro finding that M2 macrophages exhibit increased phagocytosis of rituximab-opsonized tumor cells.
“So overall, what we’re seeing is that . . . the negative influence of TAMs can be overcome with rituximab use,” she summarized.
Dr Matsuki and her colleagues also looked at the patients’ lymphocyte-to-monocyte-ratio (LMR) because TAMs partly arise from peripheral blood monocytes.
The team found that having an LMR higher than 2.77 was significantly associated with superior OS (P=0.03) in patients who did not receive rituximab. And there was a trend toward improved OS with a higher LMR in patients who did receive the drug (P=0.07).
The investigators believe the differences they observed in the prognostic value of CD163 and LMR could be explained by the fact that TAMs are derived from both circulating monocytes and resident macrophages.
Dr Matsuki said this research has improved her group’s understanding of DLBCL, but they are still working to identify additional biomarkers associated with prognosis in this disease.
*Information in the abstract differs from that presented at the meeting.