Preprint / Version 1

Analyzing Strategies to Enhance the Efficacy of Immune Checkpoint Inhibitors for Cancer Immunotherapy

##article.authors##

  • Ananya Devkirti Sage Hill School

DOI:

https://doi.org/10.58445/rars.992

Keywords:

Cancer Immunotherapy, Multivariate Model, Clinical Trials, Immune Checkpoint Inhibitors, Combination Therapies

Abstract

The discovery of immune checkpoint inhibitors (ICIs) has been a significant breakthrough in the field of cancer immunotherapy. By blocking T-cell inhibitory signals and allowing the immune system to mount a response against cancer cells, ICIs have been used to treat patients with a variety of cancer types, including metastatic melanoma, non-small cell lung cancer, hepatocellular carcinoma, and renal cell carcinoma. Currently, the US FDA has approved three categories of checkpoint inhibitors: PD-1 inhibitors (Nivolumab, Pembrolizumab, and Cemiplimab), PD-L1 inhibitors (Atezolizumab, Avelumab and Durvalumab) and one CTLA-4 inhibitor (Ipilimumab). But despite the fact that ICIs have received success in specific cancer types, such as hematological (blood) cancers like leukemia and lymphoma, they have relatively low response rates in patients suffering from epithelial (solid) cancers, limiting their use. This paper discusses possible improvements to checkpoint inhibitor therapy, including current predictive factors for response as well as mechanisms and possible improvements to PD-1/PD-L1 and CTLA-4 inhibitors. Through an exploration of current challenges to ICI therapy, clinical trials, biomarkers like the tumor mutation burden and multivariate model, and combination therapies to improve efficacy, this review aims to provide insight into potential strategies to enhance ICIs to treat a broader spectrum of cancers, leading to a more inclusive and effective treatment. While combination therapies often demonstrate enhanced efficacy, further research must be conducted to optimize treatment specifics for each cancer type. Although this review focuses on the potential of PD-1/PD-L1 and CTLA-4 inhibitors, it overlooks other novel checkpoint targets, which could offer a more broad perspective.

References

Anagnostou, V., Niknafs, N., Marrone, K. A., Bruhm, D. C., White, J. R., Naidoo, J., Hummelink, K., Monkhorst, K., Lalezari, F., Lanis, M., Rosner, S., Reuss, J. E., Smith, K. N., Adleff, V., Rodgers, K., Belcaid, Z., Rhymee, L., Levy, B., Feliciano, J., . . . Velculescu, V. E. (n.d.). Multimodal genomic features predict outcome of immune checkpoint blockade in non-small-cell lung cancer. Nature Cancer, 1(1), 99–111. https://doi.org/10.1038/s43018-019-0008-8

Ansell, S. M., Lesokhin, A. M., Borrello, I., Halwani, A., Scott, E. C., Gutierrez, M., Schuster, S. J., Millenson, M., Cattry, D., Freeman, G. J., Rodig, S. J., Chapuy, B., Ligon, A. H., Zhu, L., Grosso, J. F., Kim, S. Y. O., Timmerman, J. M., Shipp, M. A., & Armand, P. (2015). PD-1 Blockade with Nivolumab in Relapsed or Refractory Hodgkin’s Lymphoma. The New England Journal of Medicine, 372(4), 311–319. https://doi.org/10.1056/nejmoa1411087

Bagley, S., Kothari, S., Aggarwal, C., Bauml, J., Alley, E., Evans, T. L., Kosteva, J. A., Ciunci, C., Gabriel, P., Thompson, J. C., Stonehouse-Lee, S., Sherry, V. E., Gilbert, E., Eaby-Sandy, B., Mutale, F., DiLullo, G. A., Cohen, R. B., Vachani, A., & Langer, C. J. (2017). Pretreatment neutrophil-to-lymphocyte ratio as a marker of outcomes in nivolumab-treated patients with advanced non-small-cell lung cancer. Lung Cancer, 106, 1–7. https://doi.org/10.1016/j.lungcan.2017.01.013

Belcaid, Z., Phallen, J., Zeng, J., See, A. P., Mathios, D., Gottschalk, C., Nicholas, S. E., Kellett, M., Ruzevick, J., Jackson, C. M., Albesiano, E., Durham, N. M., Ye, X., Tran, P. T., Tyler, B., Wong, J. W., Brem, H., Pardoll, D. M., Drake, C. G., & Lim, M. (2014). Focal Radiation Therapy Combined with 4-1BB Activation and CTLA-4 Blockade Yields Long-Term Survival and a Protective Antigen-Specific Memory Response in a Murine Glioma Model. PLOS ONE, 9(7), e101764. https://doi.org/10.1371/journal.pone.0101764

Benzon, B., Glavaris, S., Simons, B. W., Hughes, R. M., Ghabili, K., Mullane, P., Miller, R. M., Nugent, K., Shinder, B., Tosoian, J. J., Fuchs, E. J., Tran, P. T., Hurley, P. J., Vuica‐Ross, M., Schaeffer, E. M., Drake, C. G., & Ross, A. E. (2018). Combining immune check-point blockade and cryoablation in an immunocompetent hormone sensitive murine model of prostate cancer. Prostate Cancer and Prostatic Diseases, 21(1), 126–136. https://doi.org/10.1038/s41391-018-0035-z

Borghaei, H., Paz‐Ares, L., Horn, L., Spigel, D. R., Steins, M., Ready, N., Chow, L. Q., Vokes, E. E., Felip, E., Holgado, E., Barlési, F., Kohlhufl, M., Arrieta, Ó., Burgio, M. A., Fayette, J., Léna, H., Poddubskaya, E., Gerber, D. E., Gettinger, S., . . . Brahmer, J. R. (2015b). Nivolumab versus Docetaxel in Advanced Nonsquamous Non–Small-Cell Lung Cancer. The New England Journal of Medicine, 373(17), 1627–1639. https://doi.org/10.1056/nejmoa1507643

Brok, M. D., Sutmuller, R. P., Nierkens, S., Bennink, E., Frielink, C., Toonen, L. W. J., Boerman, O. C., Figdor, C. G., Ruers, T. J., & Adema, G. J. (2006). Efficient loading of dendritic cells following cryo and radiofrequency ablation in combination with immune modulation induces anti-tumour immunity. British Journal of Cancer, 95(7), 896–905. https://doi.org/10.1038/sj.bjc.6603341

Chalmers, Z. R., Connelly, C., Fabrizio, D., Ali, S. M., Ennis, R., Schrock, A. B., Campbell, B., Shlien, A., Chmielecki, J., Huang, F. W., He, Y., Sun, J., Tabori, U., Kennedy, M., Lieber, D. S., Roels, S., White, J., Otto, G. A., Ross, J. S., . . . Frampton, G. M. (2017). Analysis of 100,000 human cancer genomes reveals the landscape of tumor mutational burden. Genome Medicine, 9(1). https://doi.org/10.1186/s13073-017-0424-2

Chen, D. S., & Mellman, I. (2017e). Elements of cancer immunity and the cancer–immune set point. Nature, 541(7637), 321–330. https://doi.org/10.1038/nature21349

Chia, S., Bedard, P. L., Hilton, J., Amir, E., Gelmon, K. A., Goodwin, R., Villa, D., Cabanero, M., Tu, D., Tsao, M., & Seymour, L. (2019). A Phase Ib Trial of Durvalumab in Combination with Trastuzumab in HER2-Positive Metastatic Breast Cancer (CCTG IND.229). Oncologist, 24(11), 1439–1445. https://doi.org/10.1634/theoncologist.2019-0321

Dewan, M. Z., Galloway, A. E., Kawashima, N., DeWyngaert, J. K., Babb, J. S., Formenti, S. C., & Demaria, S. (2009). Fractionated but Not Single-Dose Radiotherapy Induces an Immune-Mediated Abscopal Effect when Combined with Anti–CTLA-4 Antibody. Clinical Cancer Research, 15(17), 5379–5388. https://doi.org/10.1158/1078-0432.ccr-09-0265

Domchek, S. M., Postel‐Vinay, S., Im, S. A., Park, Y. H., Delord, J. P., Italiano, A., Alexandre, J., You, B., Bastian, S., Krebs, M., Wang, D., Waqar, S. N., Lanasa, M. C., Rhee, J. H., Gao, H., Rocher-Ros, V., Jones, E. V., Gulati, S., Coenen-Stass, A. M., . . . Kaufman, B. (2020). Olaparib and durvalumab in patients with germline BRCA-mutated metastatic breast cancer (MEDIOLA): an open-label, multicentre, phase 1/2, basket study. The Lancet Oncology, 21(9), 1155–1164. https://doi.org/10.1016/s1470-2045(20)30324-7

Dummer, R., Long, G. V., Robert, C., Tawbi, H., Flaherty, K. T., Ascierto, P. A., Nathan, P., Rutkowski, P., Леонов, О. В., Dutriaux, C., Mandalà, M., Lorigan, P., Ferrucci, P. F., Grob, J., Meyer, N., Gogas, H., Stroyakovskiy, D., Arance, A., Brase, J. C., . . . Schadendorf, D. (2022). Randomized Phase III trial evaluating spartalizumab plus Dabrafenib and trametinib forBRAFV600–Mutant Unresectable or metastatic melanoma. Journal of Clinical Oncology, 40(13), 1428–1438. https://doi.org/10.1200/jco.21.01601

Eroglu, Z., Zaretsky, J. M., Hu‐Lieskovan, S., Kim, D. W., Algazi, A. P., Johnson, D. B., Liniker, E., Kong, B., Munhoz, R. R., Rapisuwon, S., Gherardini, P. F., Chmielowski, B., Wang, X., Shintaku, I. P., Wei, C., Sosman, J. A., Joseph, R. W., Postow, M. A., Carlino, M. S., . . . Ribas, A. (2018). High response rate to PD-1 blockade in desmoplastic melanomas. Nature, 553(7688), 347–350. https://doi.org/10.1038/nature25187

Finn, R. S., Qin, S., Ikeda, M., Galle, P. R., Ducreux, M., Kim, T., Kudo, M., Бредер, В. В., Merle, P., Kaseb, A. O., Li, D., Verret, W., Xu, D., Hernandez, S., Liu, J., Huang, C., Mulla, S., Wang, Y., Lim, H. Y., . . . Cheng, A. (2020). Atezolizumab plus Bevacizumab in Unresectable Hepatocellular Carcinoma. The New England Journal of Medicine, 382(20), 1894–1905. https://doi.org/10.1056/nejmoa1915745

Garon, E. B., Rizvi, N. A., Hui, R., Leighl, N. B., Balmanoukian, A. S., Eder, J. P., Patnaik, A., Aggarwal, C., Gubens, M. A., Horn, L., Carcereny, E., Ahn, M., Felip, E., Lee, J., Hellmann, M. D., Hamid, O., Goldman, J. W., Soria, J., Dolled‐Filhart, M., . . . Gandhi, L. (2015b). Pembrolizumab for the treatment of Non–Small-Cell lung cancer. The New England Journal of Medicine, 372(21), 2018–2028. https://doi.org/10.1056/nejmoa1501824

Goodman, A. M., Kato, S., Bazhenova, L., Patel, S. P., Frampton, G. M., Miller, V. A., Stephens, P. J., Daniels, G. A., & Kurzrock, R. (2017b). Tumor mutational burden as an independent predictor of response to immunotherapy in diverse cancers. Molecular Cancer Therapeutics, 16(11), 2598–2608. https://doi.org/10.1158/1535-7163.mct-17-0386

Hayes, D. F. (2014). Biomarker validation and testing. Molecular Oncology, 9(5), 960–966. https://doi.org/10.1016/j.molonc.2014.10.004

Heitzer, E., Ulz, P., & Geigl, J. B. (2015). Circulating tumor DNA as a liquid biopsy for cancer. Clinical Chemistry, 61(1), 112–123. https://doi.org/10.1373/clinchem.2014.222679

Hellmann, M., Nathanson, T., Rizvi, H., McGranahan, N., Snyder, A., & Wolchok, J. (2018). Genomic Features of Response to Combination Immunotherapy in Patients with Advanced Non- Small-Cell Lung Cancer. Cell, 33(5), 843–852. https://doi.org/10.1016/j.ccell.2018.03.018

Hodi, F. S., O’Day, S., McDermott, D. F., Weber, R., Sosman, J. A., Haanen, J. B., González, R., Robert, C., Schadendorf, D., Hassel, J. C., Akerley, W., Van Den Eertwegh, A. J., Lutzky, J., Lorigan, P., Vaübel, J., Linette, G. P., Hogg, D., Ottensmeier, C., Lebbé, C., . . . Urba, W. J. (2010b). Improved Survival with Ipilimumab in Patients with Metastatic Melanoma. The New England Journal of Medicine, 363(8), 711–723. https://doi.org/10.1056/nejmoa1003466

Iranzo, P., Callejo, A., Assaf, J., Molina, G., Lopez, D. E., García-Illescas, D., Pardo, N., Navarro, A., Martinez-Martí, A., Cedrés, S., Carbonell, C., Frigola, J., Amat, R., & Felip, E. (2022). Overview of Checkpoint inhibitors Mechanism of action: Role of Immune-Related Adverse Events and their Treatment on progression of underlying cancer. Frontiers in Medicine, 9. https://doi.org/10.3389/fmed.2022.875974

Jacob, J. B., Jacob, M. K., & Parajuli, P. (2021b). Review of immune checkpoint inhibitors in immuno-oncology. In Advances in pharmacology (pp. 111–139). https://doi.org/10.1016/bs.apha.2021.01.002

Janjigian, Y. Y., Kawazoe, A., Yañez, P., Li, N., Lonardi, S., Kolesnik, O., Barajas, O., Bai, Y., Shen, L., Tang, Y., Wyrwicz, L., Xu, J., Shitara, K., Qin, S., Van Cutsem, É., Tabernero, J., Li, L., Shah, S., Bhagia, P., & Chung, H. C. (2021). The KEYNOTE-811 trial of dual PD-1 and HER2 blockade in HER2-positive gastric cancer. Nature, 600(7890), 727–730. https://doi.org/10.1038/s41586-021-04161-3

Janjigian, Y. Y., Shitara, K., Moehler, M., Garrido, M., Salman, P., Shen, L., Wyrwicz, L., Yamaguchi, K., Skoczylas, T., Bragagnoli, A. C., Liu, T., Schenker, M., Yañez, P., Tehfé, M., Kowalyszyn, R. D., Karamouzis, M. V., Brugés, R., Zander, T., Pazo‐Cid, R., . . . Ajani, J. A. (2021). First-line nivolumab plus chemotherapy versus chemotherapy alone for advanced gastric, gastro-oesophageal junction, and esophageal adenocarcinoma (CheckMate 649): a randomised, open-label, phase 3 trial. The Lancet, 398(10294), 27–40. https://doi.org/10.1016/s0140-6736(21)00797-2

Kroemer, G., Galassi, C., Zitvogel, L., & Galluzzi, L. (2022). Immunogenic cell stress and death. Nature Immunology. https://doi.org/10.1038/s41590-022-01132-2

Larkin, J., Chiarion-Sileni, V., González, R., Grob, J., Cowey, C. L., Lao, C. D., Schadendorf, D., Dummer, R., Smylie, M., Rutkowski, P., Ferrucci, P. F., Hill, A., Wagstaff, J., Carlino, M. S., Haanen, J. B., Maio, M., Márquez-Rodas, I., McArthur, G. A., Ascierto, P. A., . . . Wolchok, J. D. (2015b). Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. The New England Journal of Medicine, 373(1), 23–34. https://doi.org/10.1056/nejmoa1504030

Lee, J., Long, G. V., Boyd, S. C., Lo, S., Menzies, A. M., Tembe, V., Guminski, A., Jakrot, V., Scolyer, R. A., Mann, G. J., Kefford, R., Carlino, M. S., & Rizos, H. (2017). Circulating tumor DNA predicts response to anti-PD1 antibodies in metastatic melanoma. Annals of Oncology, 28(5), 1130–1136. https://doi.org/10.1093/annonc/mdx026

Limagne, E., Thibaudin, M., Nuttin, L., Spill, A., Dérangère, V., Fumet, J. D., Amellal, N., Peranzoni, E., Cattan, V., & Ghiringhelli, F. (2019). Trifluridine/Tipiracil plus Oxaliplatin Improves PD-1 Blockade in Colorectal Cancer by Inducing Immunogenic Cell Death and Depleting Macrophages. Cancer Immunology Research, 7(12), 1958–1969. https://doi.org/10.1158/2326-6066.cir-19-0228

Liu, P., Chen, J., Zhao, L., Hollebecque, A., Kepp, O., Zitvogel, L., & Kroemer, G. (2022). PD-1 blockade synergizes with oxaliplatin-based, but not cisplatin-based, chemotherapy of gastric cancer. OncoImmunology, 11(1). https://doi.org/10.1080/2162402x.2022.2093518

McArthur, H. L., Diab, A., Page, D. B., Yuan, J., Solomon, S. B., Sacchini, V., Comstock, C., Durack, J. C., Maybody, M., Sung, J. S., Ginsberg, A. A., Wong, P., Barlas, A., Dong, Z., Zhao, C., Blum, B., Patil, S., Neville, D., Comen, E., . . . Norton, L. (2016). A Pilot Study of Preoperative Single-Dose Ipilimumab and/or Cryoablation in Women with Early-Stage Breast Cancer with Comprehensive Immune Profiling. Clinical Cancer Research, 22(23), 5729–5737. https://doi.org/10.1158/1078-0432.ccr-16-0190

Merika, E., Syrigos, K., & Saif, M. W. (2012). Desmoplasia in pancreatic cancer. Can we fight it? Gastroenterology Research and Practice, 2012, 1–10. https://doi.org/10.1155/2012/781765

Merino, D. M., McShane, L. M., Fabrizio, D., Funari, V., Chen, S., White, J. R., Wenz, P., Baden, J., Barrett, J. C., Chaudhary, R., Chen, L., Chen, W., Cheng, J., Cyanam, D., Dickey, J. S., Gupta, L., Hellmann, M. D., Helman, E., Li, Y., . . . Allen, J. (2020). Establishing guidelines to harmonize tumor mutational burden (TMB): in silico assessment of variation in TMB quantification across diagnostic platforms: phase I of the Friends of Cancer Research TMB Harmonization Project. Journal for ImmunoTherapy of Cancer, 8(1), e000147. https://doi.org/10.1136/jitc-2019-000147

Miao, D., Margolis, C. A., Vokes, N. I., Liu, D., Taylor-Weiner, A., Wankowicz, S. A., Adeegbe, D. O., Keliher, D., Schilling, B., Tracy, A., Manos, M. P., Chau, N. G., Hanna, G. J., Polak, P., Rodig, S. J., Signoretti, S., Sholl, L. M., Engelman, J. A., Getz, G., . . . Van Allen, E. M. (2018). Genomic correlates of response to immune checkpoint blockade in microsatellite-stable solid tumors. Nature Genetics, 50(9), 1271–1281. https://doi.org/10.1038/s41588-018-0200-2

Paz-Ares, L., Luft, A., Vicente, D., Tafreshi, A., Gümüş, M., Mazières, J., Hermes, B., Şenler, F. Ç., Csőszi, T., Fülöp, A., Rodríguez-Cid, J. R., Wilson, J., Sugawara, S., Kato, T., Lee, K. H., Cheng, Y., Novello, S., Halmos, B., Li, X., . . . Investigators, K. (2018). Pembrolizumab plus Chemotherapy for Squamous Non–Small-Cell Lung Cancer. The New England Journal of Medicine, 379(21), 2040–2051. https://doi.org/10.1056/nejmoa1810865

Pfirschke, C., Engblom, C., Rickelt, S., Cortez-Retamozo, V., Garris, C., Pucci, F., Yamazaki, T., Poirier-Colame, V., Newton, A., Redouane, Y., Lin, Y., Wojtkiewicz, G. R., Iwamoto, Y., Mino‐Kenudson, M., Huynh, T. G., Hynes, R. O., Freeman, G. J., Kroemer, G., Zitvogel, L., . . . Pittet, M. J. (2016). Immunogenic chemotherapy sensitizes tumors to checkpoint blockade therapy. Immunity, 44(2), 343–354. https://doi.org/10.1016/j.immuni.2015.11.024

Polk, A., Svane, I. M., Andersson, M., & Nielsen, D. (2018). Checkpoint inhibitors in breast cancer – Current status. Cancer Treatment Reviews, 63, 122–134. https://doi.org/10.1016/j.ctrv.2017.12.008

Postow, M. A., Chesney, J., Pavlick, A. C., Robert, C., Grossmann, K. F., McDermott, D. F., Linette, G. P., Meyer, N., Giguere, J. K., Agarwala, S. S., Shaheen, M., Ernstoff, M. S., Minor, D. R., Salama, A. K., Taylor, M. H., Ott, P. A., Rollin, L., Horak, C. E., Gagnier, P., . . . Hodi, F. S. (2015b). Nivolumab and Ipilimumab versus Ipilimumab in Untreated Melanoma. The New England Journal of Medicine, 372(21), 2006–2017. https://doi.org/10.1056/nejmoa1414428

Rizvi, N. A., Hellmann, M. D., Snyder, A., Kvistborg, P., Makarov, V., Havel, J. J., Lee, W., Yuan, J., Wong, P., Ho, T. S., Miller, M. L., Rekhtman, N., Moreira, A. L., Ibrahim, F. K., Bruggeman, C., Gasmi, B., Zappasodi, R., Maeda, Y., Sander, C., . . . Chan, T. A. (2015). Mutational landscape determines sensitivity to PD-1 blockade in non–small cell lung cancer. Science, 348(6230), 124–128. https://doi.org/10.1126/science.aaa1348

Robert, C., Thomas, L., Bondarenko, I., O’Day, S., Weber, J. S., Garbe, C., Lebbe, C., Baurain, J., Testori, A., Grob, J., Davidson, N., Richards, J. M., Maio, M., Hauschild, A., Miller, W. H., Gascón, P., Lotem, M., Harmankaya, K., Ibrahim, R., . . . Wolchok, J. D. (2011c). Ipilimumab plus Dacarbazine for Previously Untreated Metastatic Melanoma. The New England Journal of Medicine, 364(26), 2517–2526. https://doi.org/10.1056/nejmoa1104621

Rubin, K. M., & Olszanski, A. J. (2020). Immune Checkpoint Inhibitor–Based therapy as a backbone in cancer treatment. Journal of the Advanced Practitioner in Oncology, 11(3). https://doi.org/10.6004/jadpro.2020.11.3.3

Sanders, S., & Debinski, W. (2020). Challenges to Successful Implementation of the Immune Checkpoint Inhibitors for Treatment of Glioblastoma. International journal of molecular sciences, 21(8), 2759. https://doi.org/10.3390/ijms21082759

Shiravand, Y., Khodadadi, F., Kashani, S. M. A., Hosseini‐Fard, S. R., Hosseini, S., Sadeghirad, H., Ladwa, R., O’Byrne, K., & Kulasinghe, A. (2022). Immune checkpoint inhibitors in cancer therapy. Current Oncology, 29(5), 3044–3060. https://doi.org/10.3390/curroncol29050247

Siva, S., MacManus, M., Martin, R. F., & Martin, O. A. (2015). Abscopal effects of radiation therapy: A clinical review for the radiobiologist. Cancer Letters, 356(1), 82–90. https://doi.org/10.1016/j.canlet.2013.09.018

Srivastava, S., & Riddell, S. R. (2018). Chimeric antigen receptor T cell therapy: Challenges to Bench-to-Bedside efficacy. Journal of Immunology, 200(2), 459–468. https://doi.org/10.4049/jimmunol.1701155

Tumeh, P. C., Harview, C. L., Yearley, J. H., Shintaku, I. P., Taylor, E. H., Robert, L., Chmielowski, B., Spasić, M., Henry, G., Ciobanu, V., West, A. N., Carmona, M., Kivork, C., Seja, E., Cherry, G., Gutiérrez, A., Grogan, T., Mateus, C., Tomasic, G., . . . Ribas, A. (2014). PD-1 blockade induces responses by inhibiting adaptive immune resistance. Nature, 515(7528), 568–571. https://doi.org/10.1038/nature13954

Weide, B., Martens, A., Hassel, J. C., Berking, C., Postow, M. A., Bisschop, K., Simeone, E., Mangana, J., Schilling, B., Di Giacomo, A. M., Brenner, N., Kähler, K. C., Heinzerling, L., Gutzmer, R., Bender, A., Gebhardt, C., Romano, E., Meier, F., Martus, P., . . . Wolchok, J. D. (2016). Baseline Biomarkers for Outcome of Melanoma Patients Treated with Pembrolizumab. Clinical Cancer Research, 22(22), 5487–5496. https://doi.org/10.1158/1078-0432.ccr-16-0127

Yang, J. C., Gadgeel, S. M., Sequist, L. V., Wu, C. L., Papadimitrakopoulou, V. A., Su, W. C., Fiore, J., Saraf, S., Raftopoulos, H., & Patnaik, A. (2019). Pembrolizumab in combination with erlotinib or gefitinib as First-Line therapy for advanced NSCLC with sensitizing EGFR mutation. Journal of Thoracic Oncology, 14(3), 553–559. https://doi.org/10.1016/j.jtho.2018.11.028

Yasuda, S., Sho, M., Yamato, I., Yoshigi, H., Wakatsuki, K., Nishiwada, S., Yagita, H., & Nakajima, Y. (2013). Simultaneous blockade of programmed death 1 and vascular endothelial growth factor receptor 2 (VEGFR2) induces synergistic anti-tumour effect in vivo. Clinical and Experimental Immunology, 172(3), 500–506. https://doi.org/10.1111/cei.12069

Yin, Q., Wu, L., Han, L., Zheng, X., Tong, R., Li, L., Bai, L., & Bian, Y. (2023). Immune-related adverse events of immune checkpoint inhibitors: a review. Frontiers in immunology, 14, 1167975. https://doi.org/10.3389/fimmu.2023.1167975

Zeng, Z., Shi, F., Zhou, L., Zhang, M. N., Chen, Y., Chang, X. J., Yin, L., Bai, W., Qu, J. H., Wang, C. P., Wang, H., Lou, M., Wang, F. S., Lv, J., & Yang, Y. (2011). Upregulation of Circulating PD-L1/PD-1 Is Associated with Poor Post-Cryoablation Prognosis in Patients with HBV-Related Hepatocellular Carcinoma. PLOS ONE, 6(9), e23621. https://doi.org/10.1371/journal.pone.0023621

Zitvogel, L., Pitt, J. M., Daillère, R., Smyth, M. J., & Kroemer, G. (2016). Mouse models in oncoimmunology. Nature Reviews Cancer, 16(12), 759–773. https://doi.org/10.1038/nrc.2016.91

Downloads

Posted

2024-03-03