Changes of Immune Cell Fractions in Patients Treated with Immune Checkpoint Inhibitors

被引：1

作者：

Kim, Hye Ryeon ^{[1
]}

Kang, Jung Hun ^{[2
]}

Kim, Sung Hyun ^{[1
]}

Kim, Seung Tae ^{[3
]}

Kim, Ilhwan ^{[4
]}

Min, Young Joo ^{[5
]}

Shin, Seong Hoon ^{[6
]}

Oh, Sung Yong ^{[1
]}

Lee, Gyeong-Won ^{[2
]}

Lee, Ji Hyun ^{[1
]}

Ji, Jun Ho ^{[7
]}

Huh, Seok Jae ^{[1
]}

Lee, Suee ^{[1
]}

机构：

[1] Dong A Univ, Dept Internal Med, Coll Med, Busan 49201, South Korea

[2] Gyeongsang Natl Univ, Gyeongsang Natl Univ Hosp, Dept Internal Med, Div Hematol Oncol,Coll Med, Jinju 52727, South Korea

[3] Sungkyunkwan Univ, Samsung Med Ctr, Dept Med, Div Hematol Oncol,Sch Med, Seoul 06351, South Korea

[4] Inje Univ, Haeundae Paik Hosp, Dept Internal Med, Div Hematol Oncol,Coll Med, Busan 48108, South Korea

[5] Univ Ulsan, Ulsan Univ Hosp, Dept Internal Med, Div Hematol Oncol,Coll Med, Ulsan 44033, South Korea

[6] Kosin Univ, Dept Internal Med, Div Med Oncol, Gospel Hosp, Busan 49267, South Korea

[7] Sungkyunkwan Univ, Samsung Changwon Hosp, Div Hematol & Oncol, Sch Med, Chang Won 51353, South Korea

来源：

CANCERS | 2022年 / 14卷 / 14期

关键词：

immune checkpoint inhibitor; immune cell fraction; response rate; progression-free survival; overall survival; PEMBROLIZUMAB; PD-L1; IMMUNOTHERAPY; CHEMOTHERAPY; NIVOLUMAB; BIOMARKER; CTLA-4;

D O I：

10.3390/cancers14143440

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Simple Summary Immune checkpoint inhibitors (ICIs) are currently widely used in many types of cancer. However, some patients could not benefit from ICIs. In addition, a standardized biomarker for predicting the efficacy of ICIs is currently unavailable. Thus, we determined whether peripheral blood immune cells could be predicting markers. In contrast with previous studies, we focused on changes in immune cell fraction and the relationship between efficacy of ICIs including response rate and survival outcomes. Results revealed significant correlations between changes in NKp46-/CD56+ NK cell fraction and treatment outcomes with ICIs. Background: With the development of immunology, immune checkpoint inhibitors (ICIs) have been widely used in various cancer treatments. Although some patients can benefit from ICIs, other patients have no response to ICIs or suffer from hyperprogression. There has been no biomarker for predicting the efficacy of ICIs. Thus, the objective of this study was to find biomarkers for predicting the efficacy of ICIs using peripheral blood. Methods: Adults patients planned to be treated with ICIs were enrolled in this study. Blood sampling was carried out before and after administration of ICIs. Changes of immune cell fraction were analyzed for each patient. Results: Among 182 patients enrolled, immune cell analysis was performed for 90 patients. The objective response rate was 14.4% (n = 13/90). The median progression-free survival (PFS) was 6.0 months (95% CI: 3.1-8.9 months), and the median overall survival (OS) was 13.9 months (95% CI: 5.6-22.2 months). Significant benefits in ORR and OS were shown for patients with increased NKp46-/CD56+ NK cells (p = 0.033 and p = 0.013, respectively). The PFS tended to be longer in these patients, although the difference was not statistically significant (p = 0.050). Conclusion: Changes of immune cell fraction before and after administration of ICIs could be a novel biomarker for predicting the efficacy of immunotherapy.

引用

页数：16

共 38 条

[1] PD-1 and PD-L1 Checkpoint Signaling Inhibition for Cancer Immunotherapy: Mechanism, Combinations, and Clinical Outcome [J].

Alsaab, Hashem O. ;

Sau, Samaresh ;

Alzhrani, Rami ;

Tatiparti, Katyayani ;

Bhise, Ketki ;

Kashaw, Sushil K. ;

Iyer, Arun K. .

FRONTIERS IN PHARMACOLOGY, 2017, 8

[2] Pembrolizumab as Second-Line Therapy for Advanced Urothelial Carcinoma [J].

Bellmunt, J. ;

de Wit, R. ;

Vaughn, D. J. ;

Fradet, Y. ;

Lee, J. -L. ;

Fong, L. ;

Vogelzang, N. J. ;

Climent, M. A. ;

Petrylak, D. P. ;

Choueiri, T. K. ;

Necchi, A. ;

Gerritsen, W. ;

Gurney, H. ;

Quinn, D. I. ;

Culine, S. ;

Sternberg, C. N. ;

Mai, Y. ;

Poehlein, C. H. ;

Perini, R. F. ;

Bajorin, D. F. .

NEW ENGLAND JOURNAL OF MEDICINE, 2017, 376 (11) :1015-1026

[3] Nivolumab versus Docetaxel in Advanced Nonsquamous Non-Small-Cell Lung Cancer [J].

Borghaei, H. ;

Paz-Ares, L. ;

Horn, L. ;

Spigel, D. R. ;

Steins, M. ;

Ready, N. E. ;

Chow, L. Q. ;

Vokes, E. E. ;

Felip, E. ;

Holgado, E. ;

Barlesi, F. ;

Kohlhaeufl, M. ;

Arrieta, O. ;

Burgio, M. A. ;

Fayette, J. ;

Lena, H. ;

Poddubskaya, E. ;

Gerber, D. E. ;

Gettinger, S. N. ;

Rudin, C. M. ;

Rizvi, N. ;

Crino, L. ;

Blumenschein, G. R. ;

Antonia, S. J. ;

Dorange, C. ;

Harbison, C. T. ;

Finckenstein, F. Graf ;

Brahmer, J. R. .

NEW ENGLAND JOURNAL OF MEDICINE, 2015, 373 (17) :1627-1639

[4] Implementing TMB measurement in clinical practice: considerations on assay requirements [J].

Buettner, Reinhard ;

Longshore, John W. ;

Lopez-Rios, Fernando ;

Merkelbach-Bruse, Sabine ;

Normanno, Nicola ;

Rouleau, Etienne ;

Penault-Llorca, Frederique .

ESMO OPEN, 2019, 4 (01)

[5] First-Line Nivolumab in Stage IV or Recurrent Non-Small-Cell Lung Cancer [J].

Carbone, D. P. ;

Reck, M. ;

Paz-Ares, L. ;

Creelan, B. ;

Horn, L. ;

Steins, M. ;

Felip, E. ;

van den Heuvel, M. M. ;

Ciuleanu, T. -E. ;

Badin, F. ;

Ready, N. ;

Hiltermann, T. J. N. ;

Nair, S. ;

Juergens, R. ;

Peters, S. ;

Minenza, E. ;

Wrangle, J. M. ;

Rodriguez-Abreu, D. ;

Borghaei, H. ;

Blumenschein, G. R. ;

Villaruz, L. C. ;

Havel, L. ;

Krejci, J. ;

Corral Jaime, J. ;

Chang, H. ;

Geese, W. J. ;

Bhagavatheeswaran, P. ;

Chen, A. C. ;

Socinski, M. A. .

NEW ENGLAND JOURNAL OF MEDICINE, 2017, 376 (25) :2415-2426

[6] The biology of human natural killer-cell subsets [J].

Cooper, MA ;

Fehniger, TA ;

Caligiuri, MA .

TRENDS IN IMMUNOLOGY, 2001, 22 (11) :633-640

[7] Immune checkpoint inhibitors: recent progress and potential biomarkers [J].

Darvin, Pramod ;

Toor, Salman M. ;

Nair, Varun Sasidharan ;

Elkord, Eyad .

EXPERIMENTAL AND MOLECULAR MEDICINE, 2018, 50 :1-11

[8] Evolution of Cancer Pharmacological Treatments at the Turn of the Third Millennium [J].

Falzone, Luca ;

Salomone, Salvatore ;

Libra, Massimo .

FRONTIERS IN PHARMACOLOGY, 2018, 9

[9] Updated Analysis From KEYNOTE-189: Pembrolizumab or Placebo Plus Pemetrexed and Platinum for Previously Untreated Metastatic Nonsquamous Non-Small-Cell Lung Cancer [J].

Gadgeel, Shirish ;

Rodriguez-Abreu, Delvys ;

Speranza, Giovanna ;

Esteban, Emilio ;

Felip, Enriqueta ;

Domine, Manuel ;

Hui, Rina ;

Hochmair, Maximilian J. ;

Clingan, Philip ;

Powell, Steven F. ;

Cheng, Susanna Yee-Shan ;

Bischoff, Helge G. ;

Peled, Nir ;

Grossi, Francesco ;

Jennens, Ross R. ;

Reck, Martin ;

Garon, Edward B. ;

Novello, Silvia ;

Rubio-Viqueira, Belen ;

Boyer, Michael ;

Kurata, Takayasu ;

Gray, Jhanelle E. ;

Yang, Jing ;

Bas, Tuba ;

Pietanza, M. Catherine ;

Garassino, Marina C. .

JOURNAL OF CLINICAL ONCOLOGY, 2020, 38 (14) :1505-+

[10] Pembrolizumab for the Treatment of Non-Small-Cell Lung Cancer [J].

Garon, Edward B. ;

Rizvi, Naiyer A. ;

Hui, Rina ;

Leighl, Natasha ;

Balmanoukian, Ani S. ;

Eder, Joseph Paul ;

Patnaik, Amita ;

Aggarwal, Charu ;

Gubens, Matthew ;

Horn, Leora ;

Carcereny, Enric ;

Ahn, Myung-Ju ;

Felip, Enriqueta ;

Lee, Jong-Seok ;

Hellmann, Matthew D. ;

Hamid, Omid ;

Goldman, Jonathan W. ;

Soria, Jean-Charles ;

Dolled-Filhart, Marisa ;

Rutledge, Ruth Z. ;

Zhang, Jin ;

Lunceford, Jared K. ;

Rangwala, Reshma ;

Lubiniecki, Gregory M. ;

Roach, Charlotte ;

Emancipator, Kenneth ;

Gandhi, Leena .

NEW ENGLAND JOURNAL OF MEDICINE, 2015, 372 (21) :2018-2028

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