抗PD-1治療延長了包括非小細胞肺癌(NSCLC)在內的轉移性腫瘤的持續反應時間以及延長了總生存期。然而，在臨床試驗中，患者對PD-1的響應率低至20%，約50%的患者不能從抗PD-1治療中獲益。於是科學家猜想存在抗腫瘤免疫亞組可能是患者對抗PD-1免疫治療效果不同的原因。那些有抗腫瘤活性的患者，本研究中的效應T細胞，具有抗腫瘤活性，在淋巴結中阻止腫瘤的生長，這些T細胞僅屬於能夠下調CD62L(CD62Llow)的T細胞。對於很多沒有特效腫瘤抗原或者肽的情況下，T細胞表麵的CD62L分子可以最為鑒定腫瘤特異性免疫細胞的替代標誌物。相關研究結果發表在6月2-6日在美國芝加哥舉行的第53屆美國臨床腫瘤學會年會(ASCO)上。
本研究共納入50例NSCLC打算接受PD-1抗體納武單抗(nivolumab)治療的患者，對其外周血單核細胞進行分析。患者接受 2周/次的3 mg/kg nivolumab治療 。用實體瘤療效評價標準(RECIST)1.1版對患者每8周治療的響應進行評估。
試驗結果發現，達到部分緩解(PR)或者穩定疾病(SD)的NSCLC患者其外周血單核細胞CD62Llow CD4+ T細胞比疾病進展(PD)的患者顯著增多 (P = 4.1x10-7) 。
CD62Llow能提供92.9%的靈敏度以及96.7%的特異性。此外，與PR患者相比，SD患者具有顯著的(p = 0.0067)調節性T細胞亞群，可以基於此對PR及SD患者進行預測。
研究結論認為，抗PD-1治療引起了PR, SD和PD患者CD4 + T的細胞的變化。
接下來正在著手CD62Llow CD4+ T的特性包括mRNA微陣列，檢查點分子和趨化因子受體等的研究。
摘要原文：
摘要編號：#11525
CD4+ T cells in PBMC to predict the outcome of anti-PD-1 therapy.
Author(s): Hiroshi Kagamu, Ou Yamaguchi, Ayako Shiono, Atsuto Mouri, Sachiko Miyauchi, Harue Utsugi, Fuyumi Nishihara, Takahiro Uchida, Yoshitake Murayama, Kunihiko Kobayashi; Niigata University, Niigata, Japan; Division of Respiratory Medicine, Saitama Medical University International Medical Center, Hidaka, Japan
Abstract Disclosures
Abstract:
Background: Antibody blockade of programmed death 1 (PD-1), has led to durable responses and significant prolongation of overall survival in metastatic cancers including non-small cell lung cancer (NSCLC). However, in clinical trials, response rates were as low as 20 %, and approximately 50 % of the patients did not achieve benefits to prolong progression free survival. These results bring us a hypothesis that there are subgroups with distinct pre-existing anti-tumor immunity resulting in different responses to anti-PD-1 therapy. We reported that effector T cells, which are capable of mediating antitumor reactivity, are primed in LNs draining growing tumors and that these T cells exclusively belong to the T cells that down-regulated CD62L (CD62Llow) subpopulation. In the absence of purified tumor antigenic proteins or peptides on many tumors, the expression of the homing molecule CD62L on T cells may serve as a surrogate marker for identifying tumor-specific immune cells. Methods: We analyzed the peripheral blood mononuclear cells (PBMC) of 50 consecutive NSCLC patients who were planned to be treated with anti-PD-1 Ab, Nivolumab after obtaining written informed consent. The patients received Nivolumab at a dose of 3 mg per kilogram of body weight every 2 weeks. Tumor response was assessed with the use of the Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1, at week 8 and every 8 weeks thereafter. Results: The NSCLC patients who achieved partial response (PR) or stable disease (SD) had significantly (p = 4.1x10-7) more CD62Llow CD4+ T cells in PBMC than progressive disease (PD) patients. The percentages of CD62Llow in CD4+ T cells provided sensitivity 92.9 %, and specificity 96.7 % to predict the patients who had PD. Moreover, SD patients had significantly (p = 0.0067) less regulatory T cell subpopulation than PR patients, thus, it was possible to predict PR from SD. Conclusions: These results show that the major differences in pre-existing immunity among PR, SD, and PD patients to anti-PD-1 Ab existed in CD4+ T cell balance between primed effector and regulatory T cells. Further characterization of CD62Llow CD4+ T cells including mRNA microarray, checkpoint molecules, and chemokine receptors is going on.
