2026年9月16~19日，由中国临床肿瘤学会（CSCO）与北京市希思科临床肿瘤学研究基金会共同主办的第29届CSCO学术年会于山东济南隆重举行。本次大会广邀海内外肿瘤学界同仁，立足真实临床痛点，传递领域前沿突破，围绕新药探索、诊疗策略优化展开多元研讨，搭建起中外肿瘤临床深度对话的学术桥梁。

大会期间，《肿瘤瞭望消化时讯》特邀南加州大学诺里斯癌症中心Heinz-Josef Lenz教授接受专访。Heinz-Josef Lenz教授立足其大会报告，聚焦MSI-H与MSS型结直肠癌的免疫治疗，系统剖析了当前最新治疗进展、临床实践中的瓶颈挑战，并展望了未来精准治疗的发展方向。现将访谈精粹整理如下。

Heinz-Josef Lenz教授：突破结直肠癌免疫治疗瓶颈，探索MSI与MSS精准治疗新路径丨2026 CSCO

Heinz-Josef Lenz 教授

我认为我们在高度微卫星不稳定（MSI-H）型肿瘤的治疗上已经取得了显著进展。这类肿瘤对免疫检查点抑制剂非常敏感，包括PD-1或PD-L1抑制剂。最新数据显示，与单独使用PD-1抑制剂相比，CTLA-4与PD-1抑制剂的联合使用疗效更优、效果更好。我们从中认识到，CTLA-4在MSI-H以及微卫星稳定（MSS）型肿瘤的免疫治疗中均可发挥重要作用。

非常关键的一点是，我们必须认识到治疗顺序的重要性。针对MSI-H型肿瘤患者，需要一开始就使用免疫治疗，而不能等到后线治疗。因此，对每一位新确诊的转移性结肠癌患者进行MSI状态、KRAS突变、BRAF突变以及HER2扩增的检测是绝对关键的。因为只有基于这种分子分型，才能给予患者最有效、最精准的治疗。切勿等到后线治疗再使用，否则会丧失疗效。

我认为突破之一是在MSS型肿瘤领域。Fc工程化CTLA-4抗体或掩蔽型CTLA-4抗体在以往被认为对免疫检查点抑制剂耐药的MSS肿瘤中展现出了疗效。然而，这些工程化CTLA-4抗体与PD-1抑制剂的联合使用，在肝外疾病中表现出了高效性；但肝脏转移瘤由于免疫抑制微环境的存在，反应并不理想。这些研究仍在进行中，并为真正开发MSS的免疫治疗铺平了道路。

另一项突破体现在新辅助治疗领域。MSI-H型直肠癌患者从免疫检查点抑制剂中获益显著，他们不仅获得了高达100%的临床完全缓解率，还避免了需要造口的外科手术、化疗或放疗。这意味着患者实际上规避了许多与这些局部区域治疗相关的并发症。

Q1：We noticed that you shared the latest advances in immunotherapy for colorectal cancer at this conference. Could you please, in the context of your presentation, introduce several of the most groundbreaking innovative therapies or clinical studies? What far-reaching impact will these advances have on current clinical practice?

Prof. Heinz-Josef Lenz：I think we have made significant progress for the MSI-H tumors. They are very sensitive to immune checkpoint inhibitors, not only the PD-1 or PD-L1 inhibitors. But recent data showed that the combination of CTLA-4 and PD-1 inhibitors is better and more effective compared with PD-1 inhibitors alone. I think what we have learned is that CTLA-4 plays a significant role in immunotherapy for MSI-H, as well as for MSS.

I think what has been very important to recognize is that the sequence of treatments matters. When you have an MSI-H tumor, you need to start with immunotherapy and don't wait for later lines of treatment. So it's absolutely critical to test every patient with newly diagnosed colon cancer with metastatic disease for MSI status, KRAS mutation, BRAF mutation and HER2 amplification, because it is absolutely important that, with this molecular characterization, the most effective treatment is given to the patient. Do not wait for later lines of treatment, because you lose efficacy.

I think one of the breakthroughs is in microsatellite stable tumors where Fc-engineered CTLA-4 antibodies or masked CTLA-4 antibodies show efficacy in MSS tumors which have been known to be resistant to immune checkpoint inhibitors. But the combination of these engineered CTLA-4 antibodies with PD-1 shows high efficacy in extrahepatic disease; liver metastatic disease does not really respond very well because of the immunosuppressive environment. These studies are ongoing and have paved the way in order to really develop immunotherapy for MSS.Another breakthrough is the neoadjuvant setting. Patients with MSI-Hrectal cancer benefit dramatically from immune checkpoint inhibitors not only do they have a high rate of complete clinical response up to one hundred percent, but these patients are spared from any surgery requiring a stoma, any chemotherapy, or any radiation, which means they actually avoid a lot of complications associated with these locoregional treatments.

Heinz-Josef Lenz 教授

我认为最大的瓶颈是并非所有患者都会接受检测。另一个瓶颈是检测结果的可靠性。免疫组化或二代测序可能具有不同的灵敏度。我们从大型随机试验中得知，两者的不一致率可能高达20%。因此，拥有一个免疫组化结果值得信赖的优质病理实验室绝对关键。根据ESMO指南以及我个人的临床实践，我会同时进行二代测序和免疫组化，以确保MSI检测结果的可靠性。

另一个有趣的发现——这不算瓶颈，而是一个挑战——无论是单药还是联合治疗，我们在转移性患者中观察到了约30%~35%的临床完全缓解率。我们目前尚不清楚这30%的患者究竟是哪部分人群。如果我们能提前识别他们，就不需要对所有患者都采用联合治疗，这意味着仅给予单药治疗时毒性会更低。我们在临床上使用CTLA-4抗体的方法已经取得了长足进步，能够有效管理和避免毒性。重要的是，我们仅需低剂量使用4个周期的CTLA-4抗体，就能维持高效的抗肿瘤作用。

对于MSS型肿瘤，目前我们尚无获批的免疫治疗药物。但正在进行的工程化CTLA-4抗体联合PD-1抑制剂的研究显示出了令人鼓舞的结果，缓解率可达30%~35%。我认为我们很有机会在未来拥有获批用于治疗转移性及局部晚期MSS型结直肠癌的免疫疗法。在中国，也有使用这些CTLA-4抗体治疗MSS型肿瘤患者的类似经验。我认为，进一步提高这些联合疗法疗效的机会还有很多。来自中国的研究表明，联合COX-2抑制剂可以进一步提升疗效。我相信还有许多潜在的新型联合策略，能够增强MSS型肿瘤免疫治疗的疗效。

Q2：Despite the progress made, precision treatment for colorectal cancer still faces challenges. What do you think are the primary bottlenecks limiting the improvement of immunotherapy efficacy in MSI and MSS patients? In your view, what emerging targets or combination strategies hold clinical translation potential to help overcome these bottlenecks?

Prof. Heinz-Josef Len ：I think the biggest bottleneck is that patients will be tested. Another bottleneck is how reliable the test results are. Immunohistochemistry or next-generation sequencing can have different sensitivities. We know from big randomized trials that the discordance can be up to twenty percent. So it's absolutely critical that you have a good pathology laboratory that you can trust the immunohistochemistry. In the ESMO guidelines and in my practice I do both next-generation sequencing and immunohistochemistry just to be assured that I can rely on MSI testing.

The other interesting finding, it's not a bottleneck but a challenge, is that with either monotherapy or combination treatment, we see about thirty to thirty-five percent complete clinical response in patients with metastatic disease. We don't know who these thirty percent are, because if we could, we would not need combination treatment in all patients, which would mean less toxicity when only monotherapy is given. We have come a long way in how we treat and use CTLA-4 antibodies in our clinic to manage and avoid toxicities. Importantly, we need only four cycles of CTLA-4 antibodies at a low dose to maintain the high efficacy.

For MSS, we have no approved immune therapeutic agents, but ongoing studies with the engineered CTLA-4 in combination with PD-1 show very promising results with response rate up to thirty to thirty-five percent range. I think there is a good chance that we will have approved immunotherapies for metastatic and possible locally advanced MSS CRC. And in China you have similar experiences with these CTLA-4 antibodies in MSS. I think there are a lot of opportunities to further increase efficacy of these combination. Studies from China show that COX-2 inhibitors in combination can further increase efficacy. I think there are a lot of potential novel combinations which may increase the efficacy of immunotherapy in MSS tumors.

Heinz-Josef Lenz 教授

是的，目前有很多正在进行的临床试验，旨在将双特异性抗体形式的免疫检查点抑制剂，联合化疗（伴或不伴贝伐珠单抗）推进到一线治疗。双特异性抗体的阳性试验将改变MSS型患者群体一线治疗的模式。早期数据显示，在一线MSS型转移性结直肠癌中，双特异性抗体的缓解率可达70%。同时，我们也投入了大量精力，并开展了大量研究，以识别哪些MSS型患者能从一线免疫治疗中获益最多。我对此非常乐观，相信我们将会看到更有效且毒性更低的免疫疗法问世。例如，我的研究团队正在致力于开发新型化合物，以提高免疫检查点抑制剂的疗效。我认为未来的方向将是利用肿瘤微环境中的分子组成和细胞因子网络，为MSS型结直肠癌患者寻找更好的治疗靶点。

Q3：Looking ahead, could you share which directions your team is currently exploring or will prioritize in the future? For example, biomarker stratification, novel immunotherapy, or special population expansion, to further advance the precision treatment of colorectal cancer?

Prof. Heinz-Josef Lenz：Yeah, there are a lot of ongoing clinical trials, you know, moving the immune checkpoint inhibitor in the form of bispecific antibodies into first line with chemo with or without bevacizumab. Positive trials with bispecific antibodies will change the paradigm of how we treat patients in the MSS patient population in the first line. Early data suggest high response rate up to seventy percent in 1L MSS mCRC with bispecific antibodies. There is also a lot of effort and ongoing research to identify patients who benefit most from immunotherapy in MSS in first line. I'm very optimistic that we will see more effective and less toxic immune therapies for our patients.

For example, my research group is working on novel compounds to improve the efficacy of immune checkpoint inhibitors. I think the future will be utilizing the molecular make up and the cytokine networking within the tumor microenvironment to find better targets in patients with MSS colorectal cancer.

专家简介

Heinz-Josef Lenz