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肿瘤部位的免疫抑制是逃避全身反应的机制吗?

Is immunosuppression at the tumor site mechanism of evasion of a systemic response?

作者信息

Karakousis Constantine P, Sharma Sanjay, Brooks Stephen P

机构信息

State University of New York at Buffalo, Kaleida Health, Buffalo, NY 14209, USA.

出版信息

J Med. 2003;34(1-6):3-14.

Abstract

BACKGROUND

Some of the questions still open to investigation are: 1) Does the clinical appearance of a tumor nodule require a prior overwhelming of a systemic host response? 2) Does a palpable growing tumor cause host immunosuppression?

MATERIALS AND METHODS

Observation of tumor growth and regression in syngeneic and allogeneic murine models under various experimental conditions. Autopsy studies of allogeneic mice with terminal progressive tumor growth.

RESULTS

In syngeneic systems, the take of a threshold tumor inoculum is not facilitated by the contralateral take and growth of a simultaneously injected ten-fold larger inoculum. In syngeneic models with a growing tumor, implantation of a threshold inoculum of the same tumor on the contralateral side is not facilitated, actually it is significantly suppressed (p > or = 0.003), compared to control mice. In early or moderately advanced stages of allogeneic tumor growth, a contralateral threshold inoculum is not facilitated, it is modestly suppressed (p = 0.04 and P = 0.05). A skin graft from the strain syngeneic to the growing tumor is rejected as rapidly in mice bearing a progressive growth as in mice without tumor or prior contact with the latter. Autopsy studies of allogeneic mice moribund from locally progressive B16 melanoma (known to metastasize early on and widely in the syngeneic host) revealed that 50% of mice had no detectable metastases, while 20% had a single pulmonary metastasis and 30% had multiple pulmonary metastases.

CONCLUSIONS

The initial appearance and growth of a tumor nodule does not involve overwhelming of a putative systemic host response. There is no systemic (general or specific) immunosuppression caused by a progressive tumor in its early or intermediate stages which apparently succeeds in growing through a local immunosuppression at its site of growth.

摘要

背景

仍有待研究的一些问题如下:1)肿瘤结节的临床表现是否需要先前全身性宿主反应的压倒性作用?2)可触及的生长肿瘤是否会导致宿主免疫抑制?

材料与方法

在各种实验条件下观察同基因和异基因小鼠模型中肿瘤的生长和消退情况。对终末期肿瘤进行性生长的异基因小鼠进行尸检研究。

结果

在同基因系统中,同时注射的十倍大接种物在对侧的接种和生长并不能促进阈值肿瘤接种物的接种。在肿瘤生长的同基因模型中,与对照小鼠相比,在对侧植入相同肿瘤的阈值接种物并未得到促进,实际上受到了显著抑制(p≥0.003)。在异基因肿瘤生长的早期或中度进展阶段,对侧阈值接种物未得到促进,受到适度抑制(p = 0.04和P = 0.05)。与肿瘤同基因品系的皮肤移植在肿瘤进行性生长的小鼠中被排斥的速度与未患肿瘤或先前未接触过肿瘤的小鼠一样快。对因局部进行性B16黑色素瘤(已知在同基因宿主中早期广泛转移)而濒死的异基因小鼠进行尸检研究发现,50%的小鼠没有可检测到的转移,而20%有单个肺转移,30%有多个肺转移。

结论

肿瘤结节的初始出现和生长并不涉及假定的全身性宿主反应的压倒性作用。在其早期或中期,进行性生长的肿瘤不会引起全身性(一般或特异性)免疫抑制,显然它是通过在其生长部位的局部免疫抑制成功生长的。

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