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Explore where and how therapy acts on the immune process and tumor progression
Explore the Mechanism of Disease and Mechanism of Action
Mechanism of Disease
There is a complex interplay between the tumor and the immune system that impacts the fate of tumor cells.1-3
Stages of Tumor Progression
Despite the immune system's efforts, tumor cells may develop oncogenic mechanisms that enable their survival and progression.2
APC=antigen presenting cell.
Stages of Immune Process
The immune system can normally detect and eliminate cancer cells through processes occurring within a repeating cycle.1
Mechanism of Action
Choose your treatment type within a specific tumor to view MOA10
Non-Small Cell Lung Cancer (NSCLC)
Metastatic/Recurrent or Early-Stage
This graphic is for demonstration purposes only. The illustrated mechanisms may vary for each patient and may not directly correlate with clinical significance. Furthermore, additional mechanisms may exist for these therapies that are not depicted in this illustration.
PD-1=programmed cell death protein-1.
OPDIVO, in combination with platinum-doublet chemotherapy, is indicated as neoadjuvant treatment of adult patients with resectable (tumors ≥4 cm or node positive) non-small cell lung cancer (NSCLC).10
OPDIVO
OPDIVO helps existing T cells discover the tumor by blocking PD-1, an immune checkpoint. This process may also target normal cells.10-12
CHEMOTHERAPY
Chemotherapy directly kills rapidly dividing tumor cells by interfering with cellular replication mechanisms.13
This graphic is for demonstration purposes only. The illustrated mechanisms may vary for each patient and may not directly correlate with clinical significance. Furthermore, additional mechanisms may exist for these therapies that are not depicted in this illustration.
PD-1=programmed cell death protein-1.
OPDIVO, in combination with platinum-doublet chemotherapy, is indicated for the neoadjuvant treatment of adult patients with resectable (tumors ≥4 cm or node positive) NSCLC and no known epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) rearrangements, followed by single-agent OPDIVO as adjuvant treatment after surgery.10
OPDIVO
OPDIVO helps existing T cells discover the tumor by blocking PD-1, an immune checkpoint. This process may also target normal cells.10-12
CHEMOTHERAPY
Chemotherapy directly kills rapidly dividing tumor cells by interfering with cellular replication mechanisms.13
This graphic is for demonstration purposes only. The illustrated mechanisms may vary for each patient and may not directly correlate with clinical significance.
1L=first-line; ALK=anaplastic lymphoma kinase; CTLA-4=cytotoxic T-lymphocyte antigen 4; EGFR=epidermal growth factor receptor; PD-1=programmed cell death protein-1; PD-L1=programmed death-ligand 1; Treg=regulatory T cell.
OPDIVO + YERVOY is indicated for the first-line treatment of adult patients with metastatic NSCLC whose tumors express PD-L1 (≥1%) as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations.10
YERVOY in combination with OPDIVO harnesses the immune system to help destroy tumor cells and defend with memory cells. The potentially synergistic mechanisms make it possible to deliver an enhanced anti-tumor response greater than the effects of either antibody alone.10,14-21
OPDIVO
OPDIVO helps existing T cells discover the tumor by blocking PD-1, an immune checkpoint. This process may also target normal cells.10-12
YERVOY
YERVOY blocks the immune checkpoint CTLA-4, which helps activate and proliferate cytotoxic T cells (that may infiltrate the tumor) and also suppresses Treg function.16,22 This process may also target normal cells.16,22 Some of the T cells stimulated by YERVOY can become memory T cells. Memory T cells may allow for a long-term immune response.14-19
This graphic is for demonstration purposes only. The illustrated mechanisms may vary for each patient and may not directly correlate with clinical significance. Furthermore, additional mechanisms may exist for these therapies that are not depicted in this illustration.
1L=first-line; ALK=anaplastic lymphoma kinase; CTLA-4=cytotoxic T-lymphocyte antigen 4; EGFR=epidermal growth factor receptor; PD-1=programmed cell death protein-1; Treg=regulatory T cell.
OPDIVO, in combination with ipilimumab and 2 cycles of platinum-doublet chemotherapy, is indicated for the 1L treatment of adult patients with metastatic or recurrent NSCLC, with no EGFR or ALK genomic tumor aberrations.10
YERVOY in combination with OPDIVO harnesses the immune system to help destroy tumor cells and defend with memory cells. The potentially synergistic mechanisms make it possible to deliver an enhanced anti-tumor response greater than the effects of either antibody alone.10,14-21
OPDIVO
OPDIVO helps existing T cells discover the tumor by blocking PD-1, an immune checkpoint. This process may also target normal cells.10-12
YERVOY
YERVOY blocks the immune checkpoint CTLA-4, which helps activate and proliferate cytotoxic T cells (that may infiltrate the tumor) and also suppresses Treg function.16,22 This process may also target normal cells.16,22 Some of the T cells stimulated by YERVOY can become memory T cells. Memory T cells may allow for a long-term immune response.14-19
CHEMOTHERAPY
Chemotherapy directly kills rapidly dividing tumor cells by interfering with cellular replication mechanisms.13
This graphic is for demonstration purposes only. The illustrated mechanisms may vary for each patient and may not directly correlate with clinical significance.
2L=second-line; ALK=anaplastic lymphoma kinase; EGFR=epidermal growth factor receptor; PD-1=programmed cell death protein-1.
OPDIVO is indicated for the treatment of adult patients with metastatic NSCLC with progression on or after platinum-based chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving OPDIVO.10
OPDIVO
OPDIVO helps existing T cells discover the tumor by blocking PD-1, an immune checkpoint. This process may also target normal cells.10-12
Renal Cell Carcinoma (RCC)
Advanced
This graphic is for demonstration purposes only. The illustrated mechanisms may vary for each patient and may not directly correlate with clinical significance.
1L=first-line; CTLA-4=cytotoxic T-lymphocyte antigen 4; PD-1=programmed cell death protein-1; Treg=regulatory T cell.
OPDIVO + YERVOY is indicated for 1L treatment of adult patients with intermediate or poor risk advanced RCC.10
YERVOY in combination with OPDIVO harnesses the immune system to help destroy tumor cells and defend with memory cells. The potentially synergistic mechanisms make it possible to deliver an enhanced anti-tumor response greater than the effects of either antibody alone.10,14-21
OPDIVO
OPDIVO helps existing T cells discover the tumor by blocking PD-1, an immune checkpoint. This process may also target normal cells.10-12
YERVOY
YERVOY blocks the immune checkpoint CTLA-4, which helps activate and proliferate cytotoxic T cells (that may infiltrate the tumor) and also suppresses Treg function.16,22 This process may also target normal cells.16,22 Some of the T cells stimulated by YERVOY can become memory T cells. Memory T cells may allow for a long-term immune response.14-19
This graphic is for demonstration purposes only. The illustrated mechanisms may vary for each patient and may not directly correlate with clinical significance. Furthermore, additional mechanisms may exist for these therapies that are not depicted in this illustration.
*MET, VEGFR-1, -2 and -3, AXL, RET, ROS1, TYRO3, MER, KIT, TRKB, FLT-3, and TIE-2.23
1L=first-line; AXL=AXL receptor tyrosine kinase; FLT-3=fms-like tyrosine kinase 3; KIT=KIT proto-oncogene receptor tyrosine kinase; MER=mer receptor tyrosine kinase; MET=mesenchymal epithelial transition factor receptor; PD-1=programmed cell death protein-1; RET=tyrosine kinase receptor rearranged during transfection; ROS1=receptor tyrosine kinase (encoded by the gene ROS1); TIE-2=tyrosine-protein kinase receptor tie-2; TRKB=tropomyosin receptor kinase B; TYRO3=tyrosine-protein kinase receptor TYRO3; VEGFR-1=vascular endothelial growth factor 1; VEGFR-2=vascular endothelial growth factor 2; VEGFR-3=vascular endothelial growth factor 3.
OPDIVO + CABOMETYX is indicated for 1L treatment of adult patients with advanced RCC.10
OPDIVO
OPDIVO helps existing T cells discover the tumor by blocking PD-1, an immune checkpoint. This process may also target normal cells.10-12
CABOMETYX
In-vitro biochemical and/or cellular assays have shown that CABOMETYX inhibits the activity of receptor tyrosine kinases* that are involved in both normal cellular function and pathologic processes such as oncogenesis, metastasis, tumor angiogenesis, drug resistance, and maintenance of the tumor microenvironment.23
This graphic is for demonstration purposes only. The illustrated mechanisms may vary for each patient and may not directly correlate with clinical significance.
2L=second-line; PD-1=programmed cell death protein-1.
OPDIVO is indicated for the treatment of adult patients with advanced RCC who have received prior anti-angiogenic therapy.10
OPDIVO
OPDIVO helps existing T cells discover the tumor by blocking PD-1, an immune checkpoint. This process may also target normal cells.10-12
Gastroesophageal Cancers
Metastatic and Adjuvant
This graphic is for demonstration purposes only. The illustrated mechanisms may vary for each patient and may not directly correlate with clinical significance.
GEJ=gastroesophageal junction; PD-1=programmed cell death protein-1.
OPDIVO is indicated for the adjuvant treatment of completely resected esophageal or gastroesophageal junction cancer with residual pathologic disease in adult patients who have received neoadjuvant chemoradiotherapy (CRT).10
OPDIVO
OPDIVO helps existing T cells discover the tumor by blocking PD-1, an immune checkpoint. This process may also target normal cells.10-12
This graphic is for demonstration purposes only. The illustrated mechanisms may vary for each patient and may not directly correlate with clinical significance. Furthermore, additional mechanisms may exist for these therapies that are not depicted in this illustration.
1L=first-line; CPS=combined positive score; GEJ=gastroesophageal junction; PD-1=programmed cell death protein-1; PD-L1=programmed death-ligand 1.
OPDIVO, in combination with fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the treatment of adult patients with advanced or metastatic gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma whose tumors express PD-L1 (≥1%).10
OPDIVO
OPDIVO helps existing T cells discover the tumor by blocking PD-1, an immune checkpoint. This process may also target normal cells.10-12
CHEMOTHERAPY
Chemotherapy directly kills rapidly dividing tumor cells by interfering with cellular replication mechanisms.13
This graphic is for demonstration purposes only. The illustrated mechanisms may vary for each patient and may not directly correlate with clinical significance.
2L=second-line; PD-1=programmed cell death protein-1.
OPDIVO is indicated for the treatment of adult patients with unresectable advanced, recurrent, or metastatic ESCC after prior fluoropyrimidine- and platinum-based chemotherapy.10
OPDIVO
OPDIVO helps existing T cells discover the tumor by blocking PD-1, an immune checkpoint. This process may also target normal cells.10-12
Melanoma
Adjuvant Therapy and Advanced Disease
This graphic is for demonstration purposes only. The illustrated mechanisms may vary for each patient and may not directly correlate with clinical significance.
PD-1=programmed cell death protein-1.
OPDIVO is indicated for the adjuvant treatment of adult and pediatric patients 12 years and older with completely resected Stage IIB, Stage IIC, Stage III, or Stage IV melanoma.10
OPDIVO
OPDIVO helps existing T cells discover the tumor by blocking PD-1, an immune checkpoint. This process may also target normal cells.10-12
This graphic is for demonstration purposes only. The illustrated mechanisms may vary for each patient and may not directly correlate with clinical significance.
1L=first-line; PD-1=programmed cell death protein-1.
OPDIVO is indicated for the treatment of adult and pediatric patients 12 years and older with unresectable or metastatic melanoma.10
OPDIVO
OPDIVO helps existing T cells discover the tumor by blocking PD-1, an immune checkpoint. This process may also target normal cells.10-12
This graphic is for demonstration purposes only. The illustrated mechanisms may vary for each patient and may not directly correlate with clinical significance.
1L=first-line; CTLA-4=cytotoxic T-lymphocyte antigen 4; PD-1=programmed cell death protein-1; Treg=regulatory T cell.
OPDIVO, in combination with ipilimumab, is indicated for the treatment of adult and pediatric patients 12 years and older with unresectable or metastatic melanoma.10
YERVOY in combination with OPDIVO harnesses the immune system to help destroy tumor cells and defend with memory cells. The potentially synergistic mechanisms make it possible to deliver an enhanced anti-tumor response greater than the effects of either antibody alone.10,14-21
OPDIVO
OPDIVO helps existing T cells discover the tumor by blocking PD-1, an immune checkpoint. This process may also target normal cells.10-12
YERVOY
YERVOY blocks the immune checkpoint CTLA-4, which helps activate and proliferate cytotoxic T cells (that may infiltrate the tumor) and also suppresses Treg function.16,22 This process may also target normal cells.16,22 Some of the T cells stimulated by YERVOY can become memory T cells. Memory T cells may allow for a long-term immune response.14-19
Urothelial Carcinoma (UC)
Locally Advanced or Metastatic and Adjuvant Therapy
This graphic is for demonstration purposes only. The illustrated mechanisms may vary for each patient and may not directly correlate with clinical significance.
PD-1=programmed cell death protein-1.
OPDIVO is indicated for the adjuvant treatment of adult patients with urothelial carcinoma (UC) who are at high risk of recurrence after undergoing radical resection of UC.10
OPDIVO
OPDIVO helps existing T cells discover the tumor by blocking PD-1, an immune checkpoint. This process may also target normal cells.10-12
This graphic is for demonstration purposes only. The illustrated mechanisms may vary for each patient and may not directly correlate with clinical significance. Furthermore, additional mechanisms may exist for these therapies that are not depicted in this illustration.
PD-1=programmed cell death protein-1.
OPDIVO, in combination with cisplatin and gemcitabine, is indicated for the first-line treatment of adult patients with unresectable or metastatic urothelial carcinoma.10
OPDIVO
OPDIVO helps existing T cells discover the tumor by blocking PD-1, an immune checkpoint. This process may also target normal cells.10-12
CHEMOTHERAPY
Chemotherapy directly kills rapidly dividing tumor cells by interfering with cellular replication mechanisms.13
This graphic is for demonstration purposes only. The illustrated mechanisms may vary for each patient and may not directly correlate with clinical significance.
2L=second-line; PD-1=programmed cell death protein-1.
OPDIVO is indicated for the treatment of adult patients with locally advanced or metastatic urothelial carcinoma (UC) who have disease progression during or following platinum-containing chemotherapy or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.10
OPDIVO
OPDIVO helps existing T cells discover the tumor by blocking PD-1, an immune checkpoint. This process may also target normal cells.10-12
Other tumor types
This graphic is for demonstration purposes only. The illustrated mechanisms may vary for each patient and may not directly correlate with clinical significance.
1L=first-line; CTLA-4=cytotoxic T-lymphocyte antigen 4; PD-1=programmed cell death protein-1; Treg=regulatory T cell.
OPDIVO + YERVOY is indicated for 1L treatment of adult patients with unresectable malignant pleural mesothelioma.10
YERVOY in combination with OPDIVO harnesses the immune system to help destroy tumor cells and defend with memory cells. The potentially synergistic mechanisms make it possible to deliver an enhanced anti-tumor response greater than the effects of either antibody alone.10,14-21
OPDIVO
OPDIVO helps existing T cells discover the tumor by blocking PD-1, an immune checkpoint. This process may also target normal cells.10-12
YERVOY
YERVOY blocks the immune checkpoint CTLA-4, which helps activate and proliferate cytotoxic T cells (that may infiltrate the tumor) and also suppresses Treg function.16,22 This process may also target normal cells.16,22 Some of the T cells stimulated by YERVOY can become memory T cells. Memory T cells may allow for a long-term immune response.14-19
This graphic is for demonstration purposes only. The illustrated mechanisms may vary for each patient and may not directly correlate with clinical significance.
2L=second-line; PD-1=programmed cell death protein-1.
OPDIVO is indicated for the treatment of adult patients with recurrent or metastatic SCCHN with disease progression on or after platinum-based therapy.10
OPDIVO
OPDIVO helps existing T cells discover the tumor by blocking PD-1, an immune checkpoint. This process may also target normal cells.10-12
1L=first-line; 2L=second-line; GEJ=gastroesophageal junction; PD-L1=programmed death-ligand 1.
References:
- Chen DS, Mellman I. Oncology meets immunology: the cancer-immunity cycle. Immunity. 2013;39(1):1-10.
- Pandya PH, Murray ME, Pollok KE, Renbarger JL. The immune system in cancer pathogenesis: potential therapeutic approaches. J Immunol Res. 2016;4273943.
- Liao S, von der Weid PY. Lymphatic system: an active pathway for immune protection. Semin Cell Dev Biol. 2015;38:83-89.
- Obst R. The timing of T cell priming and cycling. Front Immunol. 2015;6:563.
- Lau LL, Jamieson BD, Somasundaram T, Ahmed R. Cytotoxic T-cell memory without antigen. Nature. 1994;369(6482):648-652.
- Martínez-Lostao L, Anel A, Pardo J. How do cytotoxic lymphocytes kill cancer cells? Clin Cancer Res. 2015;21(22):5047-5056.
- Nishida N, Yano H, Nishida T, Kamura T, Kojiro M. Angiogenesis in cancer. Vasc Health Risk Manag. 2006;2(3):213-219.
- Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144(5):646-674.
- Yilmaz M, Christofori G. Mechanisms of motility in metastasizing cells. Mol Cancer Res. 2010;8(5):629-642.
- OPDIVO [package insert]. Princeton, NJ: Bristol-Myers Squibb Company.
- Metro G, Ricciuti B, Brambilla M, et al. The safety of nivolumab for the treatment of advanced non-small cell lung cancer. Expert Opin Drug Saf. 2017;16(1):101-109.
- Byrne EH, Fisher DE. Immune and molecular correlates in melanoma treated with immune checkpoint blockade. Cancer. 2017;123(S11):2143-2153.
- Zhao J. Cancer stem cells and chemoresistance: the smartest survives the raid. Pharmacol Ther. 2016;160:145-158.
- Felix J, Lambert J, Roelens M, et al. Ipilimumab reshapes T cell memory subsets in melanoma patients with clinical response. Oncoimmunology. 2016;5(7):1136045.
- Pico de Coaña Y, Wolodarski M, Poschke I, et al. Ipilimumab treatment decreases monocytic MDSCs and increases CD8 effector memory T cells in long-term survivors with advanced melanoma. Oncotarget. 2017;8(13):21539-21553.
- Weber JS, Hamid O, Chasalow SD, et al. Ipilimumab increases activated T cells and enhances humoral immunity in patients with advanced melanoma. J Immunother. 2012;35(1):89-97.
- Ansell SM, Hurvitz SA, Koenig PA, et al. Phase I study of ipilimumab, an anti–CTLA-4 monoclonal antibody, in patients with relapsed and refractory B-cell non–Hodgkin lymphoma. Clin Cancer Res. 2009;15(20):6446-6453.
- Farber DL, Yudanin NA, Restifo NP. Human memory T cells: generation, compartmentalization and homeostasis. Nature Rev Immunol. 2014;14:24-35.
- Pedicord VA, Montalvo W, Leiner IM, Allison JP. Single dose of anti–CTLA-4 enhances CD8+ T-cell memory formation, function, and maintenance. Proc Natl Acad Sci U S A. 2011;108(1):266-271.
- Buchbinder EI, Desai A. CTLA-4 and PD-1 pathways: similarities, differences, and implications of their inhibition. Am J Clin Oncol. 2016;39(1):98-106.
- Selby M, Engelhardt J, Lu LS, et al. Antitumor activity of concurrent blockade of immune checkpoint molecules CTLA-4 and PD-1 in preclinical models. Poster presentation at ASCO 2013. Abstract 3061.
- YERVOY [package insert]. Princeton, NJ: Bristol-Myers Squibb Company.
- CABOMETYX [package insert]. Alameda, CA: Exelixis, Inc.