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Autoantibodies targeting tumor-associated antigens in metastatic cancer: Sialylated IgGs as candidate anti-inflammatory antibodies.

Oaks M, Taylor S, Shaffer J - Oncoimmunology (2013)

Bottom Line: The sialylation pattern of these antibodies somehow correlates with their specificity for tumor-associated antigens, as IgGs targeting several antigens associated with infectious agents are relatively poor of sialic acid.We also show that some antibodies targeting the melanoma-associated antigen NY-ESO-1 bind to the human C-type lectin CD209 (DC-SIGN).The elucidation of the cellular and molecular pathways involved in the induction of anti-inflammatory antibodies specific for tumor-associated antigens and their function may yield important insights into how tumors evade immune detection and progress.

View Article: PubMed Central - PubMed

Affiliation: Aurora St. Luke's Medical Center and the Aurora Research Institute; Milwaukee, WI USA.

ABSTRACT
In addition to the well-established effector functions of IgGs, including direct cytotoxicity and antibody-dependent cellular cytotoxicity, some populations of IgGs may exert anti-inflammatory effects. Here, we describe a population of antibodies that form in the natural course of metastatic cancer and contain glycans that terminate with sialic acid. We demonstrate that both the titer of these antibodies and their level of sialylation are relatively stable throughout the progression of metastatic melanoma. The sialylation pattern of these antibodies somehow correlates with their specificity for tumor-associated antigens, as IgGs targeting several antigens associated with infectious agents are relatively poor of sialic acid. We also show that some antibodies targeting the melanoma-associated antigen NY-ESO-1 bind to the human C-type lectin CD209 (DC-SIGN). We propose that these antibodies are candidate anti-inflammatory antibodies. The presence of anti-inflammatory antibodies in cancer patients may explain, at least in part, why tumors persist and spread in the host despite strong tumor-specific humoral responses. The elucidation of the cellular and molecular pathways involved in the induction of anti-inflammatory antibodies specific for tumor-associated antigens and their function may yield important insights into how tumors evade immune detection and progress.

No MeSH data available.


Related in: MedlinePlus

Figure 1. Anti-NY-ESO-1 antibody titers in the course of this study. Titers are expressed as 1/dilution. Sample numbers indicate clinical visit in the course of treatment and vary from patient to patient. The minimum interval between sequential samples was one month. The maximum time interval between entry into the study and study completion was 16 mo.
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Figure 1: Figure 1. Anti-NY-ESO-1 antibody titers in the course of this study. Titers are expressed as 1/dilution. Sample numbers indicate clinical visit in the course of treatment and vary from patient to patient. The minimum interval between sequential samples was one month. The maximum time interval between entry into the study and study completion was 16 mo.

Mentions: We screened 168 serum samples from 80 patients with metastatic melanoma for antibodies targeting the NY-ESO-1 antigen, nine of which were positive in this respect (Table 1). Conversely, none among 33 healthy individuals was positive for NY-ESO-1-targeting autoantibodies. In melanoma patients, antibodies specific for NY-ESO-1 generally had a very high titer (>1/32,000). Of note, none of the patients initially bearing NY-ESO-1-specific autoantibodies seroconverted in the course of the observation period (Fig. 1). Likewise, the seroconversion of patients that initially had no NY-ESO-1-targeting antibodies was not observed in the course of our study (data not shown). The longitudinal evaluation of anti-NY-ESO-1 antibody titers on several of these patients documented consistent changes in a single patient. Otherwise, anti-NY-ESO-1 antibody titers were relatively stable throughout the observation period (Fig. 1).


Autoantibodies targeting tumor-associated antigens in metastatic cancer: Sialylated IgGs as candidate anti-inflammatory antibodies.

Oaks M, Taylor S, Shaffer J - Oncoimmunology (2013)

Figure 1. Anti-NY-ESO-1 antibody titers in the course of this study. Titers are expressed as 1/dilution. Sample numbers indicate clinical visit in the course of treatment and vary from patient to patient. The minimum interval between sequential samples was one month. The maximum time interval between entry into the study and study completion was 16 mo.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3716759&req=5

Figure 1: Figure 1. Anti-NY-ESO-1 antibody titers in the course of this study. Titers are expressed as 1/dilution. Sample numbers indicate clinical visit in the course of treatment and vary from patient to patient. The minimum interval between sequential samples was one month. The maximum time interval between entry into the study and study completion was 16 mo.
Mentions: We screened 168 serum samples from 80 patients with metastatic melanoma for antibodies targeting the NY-ESO-1 antigen, nine of which were positive in this respect (Table 1). Conversely, none among 33 healthy individuals was positive for NY-ESO-1-targeting autoantibodies. In melanoma patients, antibodies specific for NY-ESO-1 generally had a very high titer (>1/32,000). Of note, none of the patients initially bearing NY-ESO-1-specific autoantibodies seroconverted in the course of the observation period (Fig. 1). Likewise, the seroconversion of patients that initially had no NY-ESO-1-targeting antibodies was not observed in the course of our study (data not shown). The longitudinal evaluation of anti-NY-ESO-1 antibody titers on several of these patients documented consistent changes in a single patient. Otherwise, anti-NY-ESO-1 antibody titers were relatively stable throughout the observation period (Fig. 1).

Bottom Line: The sialylation pattern of these antibodies somehow correlates with their specificity for tumor-associated antigens, as IgGs targeting several antigens associated with infectious agents are relatively poor of sialic acid.We also show that some antibodies targeting the melanoma-associated antigen NY-ESO-1 bind to the human C-type lectin CD209 (DC-SIGN).The elucidation of the cellular and molecular pathways involved in the induction of anti-inflammatory antibodies specific for tumor-associated antigens and their function may yield important insights into how tumors evade immune detection and progress.

View Article: PubMed Central - PubMed

Affiliation: Aurora St. Luke's Medical Center and the Aurora Research Institute; Milwaukee, WI USA.

ABSTRACT
In addition to the well-established effector functions of IgGs, including direct cytotoxicity and antibody-dependent cellular cytotoxicity, some populations of IgGs may exert anti-inflammatory effects. Here, we describe a population of antibodies that form in the natural course of metastatic cancer and contain glycans that terminate with sialic acid. We demonstrate that both the titer of these antibodies and their level of sialylation are relatively stable throughout the progression of metastatic melanoma. The sialylation pattern of these antibodies somehow correlates with their specificity for tumor-associated antigens, as IgGs targeting several antigens associated with infectious agents are relatively poor of sialic acid. We also show that some antibodies targeting the melanoma-associated antigen NY-ESO-1 bind to the human C-type lectin CD209 (DC-SIGN). We propose that these antibodies are candidate anti-inflammatory antibodies. The presence of anti-inflammatory antibodies in cancer patients may explain, at least in part, why tumors persist and spread in the host despite strong tumor-specific humoral responses. The elucidation of the cellular and molecular pathways involved in the induction of anti-inflammatory antibodies specific for tumor-associated antigens and their function may yield important insights into how tumors evade immune detection and progress.

No MeSH data available.


Related in: MedlinePlus