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Role of CD8-positive cells in radioimmunotherapy utilizing (177)Lu-mAbs in an immunocompetent rat colon carcinoma model.

Elgström E, Eriksson SE, Ohlsson TG, Nilsson R, Tennvall J - EJNMMI Res (2015)

Bottom Line: Five animals in the group given anti-CD8 + RIT were sacrificed due to metastatic disease, and 4 additional animals were found to have metastases at autopsy.In the group given RIT, 4 animals developed metastatic disease, but no metastases were found in the remaining 11 animals at autopsy.The initial depletion of CD8-positive cells in our syngeneic rat colon carcinoma model resulted in a higher frequency of animals developing metastases.

View Article: PubMed Central - PubMed

Affiliation: Division of Oncology and Pathology, Department of Clinical Sciences, Lund University, Barngatan 2B, SE-221 85 Lund, Sweden.

ABSTRACT

Background: CD8-positive cells might play a crucial role in the therapeutic response to radiation, which has however not been investigated in radioimmunotherapy (RIT). The aim of this study was to evaluate whether cytotoxic T cells affect the response of established tumors and, above all, if they delay or prevent the development of distant metastases after RIT, using an immunocompetent syngeneic rat colon carcinoma model.

Methods: The cytotoxic T cells were depleted in 15 rats by anti-CD8 before the injection of the radioimmunoconjugate (400 MBq/kg body weight (177)Lu-BR96, which binds to the tumor-associated antigen Lewis Y). Fifteen other rats were treated with RIT only. Both groups were followed for 99 days. Blood samples were collected at least once weekly, and tumors were monitored twice weekly.

Results: Twenty-nine of the 30 animals exhibited local complete response. The non-responder was treated with anti-CD8 and RIT but succumbed later due to metastases. Five animals in the group given anti-CD8 + RIT were sacrificed due to metastatic disease, and 4 additional animals were found to have metastases at autopsy. In the group given RIT, 4 animals developed metastatic disease, but no metastases were found in the remaining 11 animals at autopsy. Thus, at the end of the study, 6 animals in the anti-CD8 + RIT group were free from metastases, while 11 were free from metastases in the group receiving RIT. CD3(+)CD4(-)CD8(+) lymphocytes were consistently depleted by the anti-CD8 treatment. The myelosuppression was otherwise similar in the two groups. The initial depletion of CD8-positive cells in our syngeneic rat colon carcinoma model resulted in a higher frequency of animals developing metastases.

Conclusions: Depletion of CD8-positive cells during RIT in an immunocompetent rat tumor model might influence the number of animals developing metastases, indicating that the immune system may be important in the long-term outcome of RIT.

No MeSH data available.


Related in: MedlinePlus

Tumor volume growth after treatment. Individual (black) and average (red bold) tumor volumes in animals treated with anti-CD8 + RIT (above) and in animals treated with RIT only (below).
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Fig1: Tumor volume growth after treatment. Individual (black) and average (red bold) tumor volumes in animals treated with anti-CD8 + RIT (above) and in animals treated with RIT only (below).

Mentions: All animals in the RIT group exhibited local complete response, defined as non-palpable tumor and no detectable tumor at dissection. In the anti-CD8 + RIT group, all animals but one showed local complete response, although this tumor initially responded well to the treatment (reduction in tumor volume of 99%). The animal not showing local complete response was sacrificed due to metastatic disease on day 45. There was no statistical difference between the groups regarding time to local complete response (Mantel-Cox test). Individual tumor volumes are presented in Figure 1.Figure 1


Role of CD8-positive cells in radioimmunotherapy utilizing (177)Lu-mAbs in an immunocompetent rat colon carcinoma model.

Elgström E, Eriksson SE, Ohlsson TG, Nilsson R, Tennvall J - EJNMMI Res (2015)

Tumor volume growth after treatment. Individual (black) and average (red bold) tumor volumes in animals treated with anti-CD8 + RIT (above) and in animals treated with RIT only (below).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4385015&req=5

Fig1: Tumor volume growth after treatment. Individual (black) and average (red bold) tumor volumes in animals treated with anti-CD8 + RIT (above) and in animals treated with RIT only (below).
Mentions: All animals in the RIT group exhibited local complete response, defined as non-palpable tumor and no detectable tumor at dissection. In the anti-CD8 + RIT group, all animals but one showed local complete response, although this tumor initially responded well to the treatment (reduction in tumor volume of 99%). The animal not showing local complete response was sacrificed due to metastatic disease on day 45. There was no statistical difference between the groups regarding time to local complete response (Mantel-Cox test). Individual tumor volumes are presented in Figure 1.Figure 1

Bottom Line: Five animals in the group given anti-CD8 + RIT were sacrificed due to metastatic disease, and 4 additional animals were found to have metastases at autopsy.In the group given RIT, 4 animals developed metastatic disease, but no metastases were found in the remaining 11 animals at autopsy.The initial depletion of CD8-positive cells in our syngeneic rat colon carcinoma model resulted in a higher frequency of animals developing metastases.

View Article: PubMed Central - PubMed

Affiliation: Division of Oncology and Pathology, Department of Clinical Sciences, Lund University, Barngatan 2B, SE-221 85 Lund, Sweden.

ABSTRACT

Background: CD8-positive cells might play a crucial role in the therapeutic response to radiation, which has however not been investigated in radioimmunotherapy (RIT). The aim of this study was to evaluate whether cytotoxic T cells affect the response of established tumors and, above all, if they delay or prevent the development of distant metastases after RIT, using an immunocompetent syngeneic rat colon carcinoma model.

Methods: The cytotoxic T cells were depleted in 15 rats by anti-CD8 before the injection of the radioimmunoconjugate (400 MBq/kg body weight (177)Lu-BR96, which binds to the tumor-associated antigen Lewis Y). Fifteen other rats were treated with RIT only. Both groups were followed for 99 days. Blood samples were collected at least once weekly, and tumors were monitored twice weekly.

Results: Twenty-nine of the 30 animals exhibited local complete response. The non-responder was treated with anti-CD8 and RIT but succumbed later due to metastases. Five animals in the group given anti-CD8 + RIT were sacrificed due to metastatic disease, and 4 additional animals were found to have metastases at autopsy. In the group given RIT, 4 animals developed metastatic disease, but no metastases were found in the remaining 11 animals at autopsy. Thus, at the end of the study, 6 animals in the anti-CD8 + RIT group were free from metastases, while 11 were free from metastases in the group receiving RIT. CD3(+)CD4(-)CD8(+) lymphocytes were consistently depleted by the anti-CD8 treatment. The myelosuppression was otherwise similar in the two groups. The initial depletion of CD8-positive cells in our syngeneic rat colon carcinoma model resulted in a higher frequency of animals developing metastases.

Conclusions: Depletion of CD8-positive cells during RIT in an immunocompetent rat tumor model might influence the number of animals developing metastases, indicating that the immune system may be important in the long-term outcome of RIT.

No MeSH data available.


Related in: MedlinePlus