臨床外科74巻8号

2019年08月発行

特集 これだけは押さえたい！—大腸癌取扱い規約・治療ガイドライン—改訂のポイント 大腸癌治療ガイドライン2019

外科医のための免疫チェックポイント阻害薬の基礎知識

著者： 江頭徹哉¹ 谷口浩也¹

所属機関： ¹国立がん研究センター東病院消化管内科

ページ範囲：P.984 - P.988

【ポイント】
◆MSI-High/dMMR大腸癌は右側結腸癌に多く，切除可能例では予後良好，切除不能例では予後不良である．
◆大腸癌を含むMSI-High/dMMR固形癌に対してペムブロリズマブが臓器横断的に承認された．
◆今後，MSS大腸癌に対しても，ほかの薬物療法や放射線療法との併用による治療効果の向上が期待される．

参考文献

1）Hampel H, Frankel WL, Martin E, et al：Screening for the Lynch syndrome（hereditary nonpolyposis colorectal cancer）. N Engl J Med 352：1851-1860, 2005

2）Wang Y, Shi C, Eisenberg R, et al：Differences in Microsatellite Instability Profiles between Endometrioid and Colorectal Cancers：A Potential Cause for False-Negative Results? J Mol Diagn 19：57-64, 2017

3）Colle R, Cohen R. Cochereau D, et al：Immunotherapy and patients treated for cancer with microsatellite instability. Bull Cancer 104：42-51, 2017

4）Walther A, Johnstone E, Swanton C, et al：Genetic prognostic and predictive markers in colorectal cancer. Nat Rev Cancer 9：489-499, 2009

5）Van Custem E, Cervantes A, Adam R, et al：ESMO consensus guidelines for the management of patients with metastatic colorectal cancer. Ann Oncol 27：1386-1422, 2016

6）Kajiwara T, et al：The Nationwide Cancer Genome Screening Project for Gastrointestinal Cancer in Japan（GI-SCREEN）：MSI-status and cancer-related genome alterations in advanced colorectal cancer（CRC）-GI-SCREEN 2013-01-CRC sub-study. J Clin Oncol 34：3573, 2016

7）Poulogiannis G, Frayling IM, Arends MJ：DNA mismatch repair deficiency in sporadic colorectal cancer and Lynch syndrome. Histopathology 56：167-179, 2010

8）Hutchins G, Southward K, Handley K, et al：Value of mismatch repair, KRAS and BRAF mutations in predicting recurrence and benefits from chemotherapy in colorectal cancer. J Clin Oncol 29：1261, 2011

9）Sargent DJ, Marsoni S, Monges G, et al：Defective mismatch repair as a predictive biomarker for lack of efficacy of fluorouracil-based adjuvant therapy in colon cancer. J Clin Oncol 28：3219-3226, 2010

10）Gavin PG, Colangelo LH, Fumagalli D, et al：Mutation Profiling and Microsatellite Instability in Stage Ⅱ and Ⅲ Colon Cancer：An Assessment of Their Prognostic and Oxaliplatin Predictive Value. Clin Cancer Res 18：6531-6541, 2012

11）Venderbosch S, Nagtegaal ID, Maughan TS, et al：Mismatch repair status and BRAF mutation status in metastatic colorectal cancer patients：a pooled analysis of CAIRO, CAIRO2, COIN, and FOCUS studies. Clin Cancer Res 20：5322-5330, 2014

12）Le DT, Uram JN, Wang H, et al：Programmed death-1 blockade in mismatch repair deficient colorectal cancer. J Clin Oncol 34（suppl）：abstr103, 2016

13）Le DT, Uram JN, Wang H, et al：PD-1 Blockade in Tumors with Mismatch-Repair Deficiency. N Engl J Med 372：2509-2520, 2015

14）Diaz LA, Marabelle A, Delord J-P, et al：Pembrolizumab therapy for microsatellite instability high（MSI-H）colorectal cancer（CRC）and non-CRC. J Clin Oncol 35（suppl）：abstr3071, 2017

15）Overman MJ, McDermott R, Leach JL, et al：Nivolumab in patients with metastatic DNA mismatch repair-deficient or microsatellite instability-high colorectal cancer（CheckMate 142）：an open-label, multicentre, phase 2 study. Lancet Oncol 18：1182-1191, 2017

16）Shahda S, Noonan AM, Bekaii-Saab TS, et al：A phase Ⅱ study of pembrolizumab in combination with mFOLFOX6 for patients with advanced colorectal cancer. J Clin Oncol 35（suppl）：abstr 3541, 2017

17）Terme M, Pernot S, Marcheteau E, et al：VEGFA-VEGFR pathway blockade inhibits tumor-induced regulatory T-cell proliferation in colorectal cancer. Cancer Res 73：539-549, 2013

18）Wölfle SJ, Strebovsky J, Bartz H, et al：PD-L1 expression on tolerogenic APCs is controlled by STAT-3. Eur J Immunol 41：413-424, 2011