Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, IBB 2310, 315 Ferst Drive NW, Atlanta, GA, 30332, USA.
Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA, 30332, USA.
Cancer Immunol Immunother. 2021 Aug;70(8):2179-2195. doi: 10.1007/s00262-020-02792-5. Epub 2021 Jan 18.
Triple negative breast cancer (TNBC) is a significant clinical problem to which immunotherapeutic strategies have been applied with limited success. Using the syngeneic E0771 TNBC mouse model, this work explores the potential for antitumor CD8 T cell immunity to be primed extratumorally in lymphoid tissues and therapeutically leveraged. CD8 T cell viability and responses within the tumor microenvironment (TME) were found to be severely impaired, effects coincident with local immunosuppression that is recapitulated in lymphoid tissues in late stage disease. Prior to onset of a locally suppressed immune microenvironment, however, CD8 T cell priming within lymph nodes (LN) that depended on tumor lymphatic drainage remained intact. These results demonstrate tumor-draining LNs (TdLN) to be lymphoid tissue niches that support the survival and antigenic priming of CD8 T lymphocytes against lymph-draining antigen. The therapeutic effects of and CD8 T cells response to immune checkpoint blockade were furthermore improved when directed to LNs within the tumor-draining lymphatic basin. Therefore, TdLNs represent a unique potential tumor immunity reservoir in TNBC for which strategies may be developed to improve the effects of ICB immunotherapy.
三阴性乳腺癌（TNBC）是一个重大的临床问题，免疫治疗策略已被应用于其中，但收效有限。本研究使用同源 E0771 TNBC 小鼠模型，探索了在肿瘤外的淋巴组织中诱导抗肿瘤 CD8 T 细胞免疫的潜力，并将其用于治疗。研究发现，肿瘤微环境（TME）中的 CD8 T 细胞活力和反应受到严重损害，这种影响与局部免疫抑制一致，而晚期疾病中的淋巴组织也存在这种抑制。然而，在局部免疫抑制微环境出现之前，依赖于肿瘤淋巴管引流的淋巴结（LN）中的 CD8 T 细胞的初始仍然完整。这些结果表明，引流肿瘤的淋巴结（TdLN）是支持 CD8 T 淋巴细胞对抗淋巴引流抗原的存活和抗原初始的淋巴组织小生境。当将免疫检查点阻断的治疗效果和 CD8 T 细胞反应靶向到肿瘤引流淋巴盆地的淋巴结时，其效果得到了进一步改善。因此，TdLN 代表了 TNBC 中一个独特的潜在肿瘤免疫库，可开发相关策略来提高 ICB 免疫治疗的效果。
