WavebreakmediaMicro/AdobeStock
Immunotherapy, in the form of immune checkpoint inhibitors (ICI), has been a recent breakthrough in the management of both early and late-stage melanoma. With the advent of immunotherapy, the 1-year survival rate for patients with metastatic disease has increased from 25% to 50%.1 ICIs have contributed to improved outcomes of treatment and prognosis of patients with different malignancies and are now served as a standard treatment for advanced melanoma.2
Recent study results revealed that treatment with combined anti-CTLA-4/anti-PD-1 results in median overall survival and a significant durability response, which is superior to that of nivolumab monotherapy and ipilimumab monotherapy.3 Also, the benefits of combined treatment were similar for patients, irrespective of their BRAFV600 mutational and PD-L1 expression status. ICIs provide a significant response in patients with brain metastasis, particularly those who are asymptomatic of malignant infiltration at the time of presentation.4 Study results also revealed that intracranial responses of combined ipilimumab/nivolumab were more than 50% in patients whose metastases have not been treated with brain radiotherapy.5 Another study found that ipilimumab/nivolumab was significantly superior to nivolumab monotherapy with a 5-year survival rate of 51% in patients with asymptomatic disease.6 In the therapeutic field of melanoma, prior immunostimulatory treatments such as interleukin-2 (IL-2) were superseded by ICIs. For high-risk, early-stage melanoma, ipilimumab was found to increase the 3-year recurrence-free rate by more than 10%.6
While surgical excision is the primary treatment for non-melanoma skin cancers (NMSCs), immunotherapy has emerged as a promising treatment option in recent years.7 In the case of NMSCs, ICIs are the most commonly used immunotherapy drugs. These drugs block proteins in cancer cells, preventing the immune system from recognizing and attacking them.8 Clinical trials have shown that ICIs such as pembrolizumab and nivolumab have high response rates and durable responses in patients with advanced NMSCs.9 These drugs have been approved by the US Food and Drug Administration for the treatment of metastatic or locally advanced squamous cell carcinoma (SCC) and basal cell carcinoma (BCC), which cannot be treated with surgery or radiation. Other types of immunotherapies for NMSCs include topical immunomodulators such as imiquimod and ingenol mebutate, which stimulate the immune system to attack cancer cells locally.10 Intralesional immunotherapy, which involves injecting an immune-stimulating substance directly into the tumor, is also being investigated as a potential treatment option. For the treatment of cutaneous SCC (cSCC), pembrolizumab and cemiplimab, two single-agent anti-PD-1 inhibitors, exhibited an overall response rate of 42% and 52% in recurrent/metastatic disease and locally advanced disease, respectively, when used as frontline, first-line treatment for advanced or metastatic cSCC that is not responsive to surgery or radiation.11 Both medications had long-lasting effects with manageable side effects. Merkle cell carcinoma (MCC), like cSCC, is a very immunogenic illness and a promising target for immunotherapy based on ICI. In pre-treated patients with advanced MCC, the JAVELIN Merkel 200 study showed that avelumab resulted in a 33.0% overall response rate and a median duration of response of 40.5 months.12 In comparison to cSCC, BCCs are at least two times more prevalent. The metastatic rate for BCCs is less than 1%, which is substantially lower than that for cSCCs and MCCs. Moreover, cemiplimab has been shown to generate a strong antitumor response in patients with locally advanced BCC.13
Biomarkers of response to immunotherapy in melanoma have been studied to help identify patients most likely to benefit from treatment and develop new therapeutic strategies. Programmed death-ligand 1 (PD-L1) is a protein expressed on the surface of some cancer cells, including melanoma.14 It interacts with the programmed death-1 (PD-1) receptor on T cells, inhibiting their activity and preventing the immune system from attacking cancer cells. Tumors with high levels of PD-L1 expression are more likely to respond to PD-1/PD-L1 checkpoint inhibitors. Tumor mutational burden (TMB) measures the number of mutations present in a tumor's DNA. High TMB is associated with an increased likelihood of response to ICIs, as these mutations may generate new tumor antigens that can be recognized by the immune system.15 TMB is naturally elevated in melanoma and correlates with better responses toimmune checkpoint inhibition depending on the severity of cancer. However, it is not regularly used as a predictor of ICI response. Melanoma responds exceedingly well to ICI; hence, a biomarker of ICI resistance may be more important than a biomarker of response in clinical care. Tumor-infiltrating lymphocytes (TILs) are immune cells that have migrated into the tumor microenvironment. Tumors with high levels of TILs are more likely to respond to immunotherapy, as they indicate an ongoing immune response against the tumor.16 The biomarkers of immunotherapy response in melanoma also include immune gene expression profiling and the gut microbiome. Gene expression profiling can be used to assess the activity of immune-related genes within the tumor microenvironment.17 Certain gene signatures have been associated with response to immunotherapy in melanoma. The composition of the gut microbiome has been shown to affect the efficacy of immune checkpoint inhibitors.18 Studies suggest that a more diverse gut microbiome is associated with a better response to immunotherapy.
Biomarkers that can help predict immunotherapy response or resistance in non-melanoma skin cancers include Interferon-gamma (IFN-) signature, Immunoscore, and Circulating tumor DNA (ctDNA). Interferon-gamma (IFN-) signature is a cytokine that plays a vital role in activating the immune system.19 Tumors with a high IFN- signature may be more likely to respond to immunotherapy. The Immunoscore is a measure of the immune cell infiltration and activation within a tumor. A higher Immunoscore may indicate a better response to immunotherapy.20 Circulating tumor DNA (ctDNA) refers to small fragments of DNA that are shed by tumor cells into the bloodstream. The presence of ctDNA may indicate the presence of residual disease, and monitoring ctDNA levels may help predict response to immunotherapy.21
Immunotherapy has revolutionized the treatment of melanoma and non-melanoma skin cancers, and research is ongoing to identify new targets and improve existing therapies. Now considered the gold standard for treating advanced melanoma, immune checkpoint inhibitors (ICIs) have helped improve the treatment and prognosis of patients with a variety of cancers. Median overall survival and a substantial, durable response are achieved with anti-CTLA-4/anti-PD-1 combination therapy. Previous immunostimulatory therapies, such as interleukin-2 (IL-2), have been replaced by immune checkpoint inhibitors in the therapeutic field of melanoma. Patients with advanced NMSCs have shown both a high response rate and long-lasting responses to immune checkpoint inhibitors like pembrolizumab and nivolumab, according to clinical trials. Immunotherapy has been shown to be effective against melanoma, and researchers have been looking at biomarkers of response to better target treatment towards patients suffering from skin cancers. PD-L1 expression, TMB, MSI, TILs, and HPV status have all been identified as potential biomarkers of response to immunotherapy in melanoma and non-melanoma skin cancers. However, additional research is needed to better understand the complex interplay between the tumor microenvironment and the immune system.
References
1. Bagchi S, Yuan R, Engleman EG. Immune checkpoint inhibitors for the treatment of cancer: Clinical impact and mechanisms of response and resistance.Annual Review of Pathology: Mechanisms of Disease. 2021;16(1):223-249. doi:https://doi.org/10.1146/annurev-pathol-042020-042741
2. Kostine M, Rouxel L, Barnetche T, et al. Rheumatic disorders associated with immune checkpoint inhibitors in patients with cancerclinical aspects and relationship with tumour response: a single-centre prospective cohort study.Annals of the Rheumatic Diseases. 2017;77(3):393-398. doi:https://doi.org/10.1136/annrheumdis-2017-212257
3. Hwang JK, Hong J, Yun CO. Oncolytic viruses and immune checkpoint inhibitors: Preclinical developments to clinical trials.International Journal of Molecular Sciences. 2020;21(22):8627. doi:https://doi.org/10.3390/ijms21228627
4. Bence C, Hofman V, Chamorey E, et al. Association of combined PD L1 expression and tumourinfiltrating lymphocyte features with survival and treatment outcomes in patients with metastatic melanoma.Journal of the European Academy of Dermatology and Venereology. 2019;34(5):984-994. doi:https://doi.org/10.1111/jdv.16016
5. Suda K. Recent Advances in cancer immunotherapy.Biomolecules. 2021;11(2):335. doi:https://doi.org/10.3390/biom11020335
6. Zimmer L, Livingstone E, Hassel JC, et al. Adjuvant nivolumab plus ipilimumab or nivolumab monotherapy versus placebo in patients with resected stage IV melanoma with no evidence of disease (IMMUNED): a randomised, double-blind, placebo-controlled, phase 2 trial.The Lancet. 2020;395(10236):1558-1568. doi:https://doi.org/10.1016/s0140-6736(20)30417-7
7. Shalhout SZ, Emerick KS, Kaufman HL, Miller DM. Immunotherapy for non-melanoma skin cancer.Current Oncology Reports. 2021;23(11). doi:https://doi.org/10.1007/s11912-021-01120-z
8. Zelin E, Maronese CA, Dri A, et al. Identifying candidates for immunotherapy among patients with non-melanoma skin cancer: A review of the potential predictors of response.Journal of Clinical Medicine. 2022;11(12):3364. doi:https://doi.org/10.3390/jcm11123364
9. Fahradyan A, Howell AC, Wolfswinkel EM, Tsuha M, Sheth P, Wong AK. Updates on the management of non-melanoma skin cancer (NMSC).Healthcare. 2017;5(4). doi:https://doi.org/10.3390/healthcare5040082
10. Cives M, Mannavola F, Lospalluti L, et al. Non-melanoma skin cancers: Biological and clinical features.International Journal of Molecular Sciences. 2020;21(15). doi:https://doi.org/10.3390/ijms21155394
11. Ascierto PA, Schadendorf D. Immunotherapy in non-melanoma skin cancer: Updates and new perspectives.Drugs in Context. 2019;8:1-6. doi:https://doi.org/10.7573/dic.212583
12. Shalhout SZ, Emerick KS, Kaufman HL, Miller DM. Immunotherapy for non-melanoma skin cancer.Current Oncology Reports. 2021;23(11). doi:https://doi.org/10.1007/s11912-021-01120-z
13. Stratigos AJ, Sekulic A, Peris K, et al. Cemiplimab in locally advanced basal cell carcinoma after hedgehog inhibitor therapy: an open-label, multi-centre, single-arm, phase 2 trial.The Lancet Oncology. 2021;22(6):848-857. doi:https://doi.org/10.1016/s1470-2045(21)00126-1
14. Berghoff AS, Ricken G, Widhalm G, et al. Tumour-infiltrating lymphocytes and expression of programmed death ligand 1 (PD-L1) in melanoma brain metastases.Histopathology. 2014;66(2):289-299. doi:https://doi.org/10.1111/his.12537
15. Jardim DL, Goodman A, de Melo Gagliato D, Kurzrock R. The challenges of tumor mutational burden as an immunotherapy biomarker.Cancer Cell. 2021;39(2):154-173. doi:https://doi.org/10.1016/j.ccell.2020.10.001
16. Paijens ST, Vledder A, de Bruyn M, Nijman HW. Tumor-infiltrating lymphocytes in the immunotherapy era.Cellular & Molecular Immunology. Published online November 2, 2020:1-18. doi:https://doi.org/10.1038/s41423-020-00565-9
17. Farberg AS, Marson JW, Glazer A, et al. Expert consensus on the use of prognostic gene expression profiling tests for the management of cutaneous melanoma: Consensus from the skin cancer prevention working group.Dermatology and Therapy. 2022;12(4):807-823. doi:https://doi.org/10.1007/s13555-022-00709-x
18. Rezasoltani S, Yadegar A, Asadzadeh Aghdaei H, Reza Zali M. Modulatory effects of gut microbiome in cancer immunotherapy: A novel paradigm for blockade of immune checkpoint inhibitors.Cancer Medicine. 2020;10(3):1141-1154. doi:https://doi.org/10.1002/cam4.3694
19. Bridge JA, Lee JC, Daud A, Wells JW, Bluestone JA. Cytokines, chemokines, and other biomarkers of response for checkpoint inhibitor therapy in skin cancer.Frontiers in Medicine. 2018;5. doi:https://doi.org/10.3389/fmed.2018.00351
20. Bruni D, Angell HK, Galon J. The immune contexture and Immunoscore in cancer prognosis and therapeutic efficacy.Nature Reviews Cancer. Published online August 4, 2020:1-19. doi:https://doi.org/10.1038/s41568-020-0285-7
21. Cabel L, Riva F, Servois V, et al. Circulating tumor DNA changes for early monitoring of anti-PD1 immunotherapy: a proof-of-concept study.Annals of Oncology. 2017;28(8):1996-2001. doi:https://doi.org/10.1093/annonc/mdx212
See the original post:
The Future of Immunotherapy Targets - Dermatology Times
- TikTok dermfluencers have medical students flocking to dermatology, where they can make half a million dollars a year and work four days a week -... - November 20th, 2024 [November 20th, 2024]
- $500,000 Pay, Predictable Hours: How Dermatology Became the It Job in Medicine - The Wall Street Journal - November 20th, 2024 [November 20th, 2024]
- Empowering Dermatology PAs Through Education and Career Support - Dermatology Times - November 20th, 2024 [November 20th, 2024]
- U.S. Dermatology Partners Announces the Opening of Stephenville, Texas Office - PR Web - November 20th, 2024 [November 20th, 2024]
- $500,000 Pay, Predictable Hours: How Dermatology Became the It Job in Medicine - Yahoo! Voices - November 20th, 2024 [November 20th, 2024]
- FRONTIER-2 Study Evaluates Safety and Efficacy of Tozorakimab in Patients with AD - Dermatology Times - November 20th, 2024 [November 20th, 2024]
- Improving Care and Innovations in Vitiligo and Atopic Dermatitis: Part 1 - Dermatology Times - November 20th, 2024 [November 20th, 2024]
- In the United States, the dermatology concentration of doctors is also noticeable.The Wall Street Jo.. - - November 20th, 2024 [November 20th, 2024]
- Dermatology Diagnostic Devices and Therapeutics Market Size, Trends and Industry Growth Forecast to 2032 - openPR - November 20th, 2024 [November 20th, 2024]
- POLL: What Topics Are You Looking Forward to at SDPA Fall 2024? - Dermatology Times - November 20th, 2024 [November 20th, 2024]
- Digital tool aims to tackle long dermatology waits - Health and Care News Scotland - November 20th, 2024 [November 20th, 2024]
- Is AI Coming for My Job?: Familiarizing Clinicians with AI Tools and Their Role in Dermatology - Dermatology Times - November 12th, 2024 [November 12th, 2024]
- Almiralls Nine-Month 2024 Results: Almirall Reports Strong Performance at Q3 2024 - Driven by Successful Commercial Execution of the Dermatology... - November 12th, 2024 [November 12th, 2024]
- Updates on the Latest Cosmetic Treatments in Medical Care - Dermatology Times - November 12th, 2024 [November 12th, 2024]
- Jenny Murase, MD: Emerging Therapies Bring Hope to Patients with Persistent Itch - Dermatology Times - November 12th, 2024 [November 12th, 2024]
- POLL: Are You Attending the Elevate-Derm West Conference? - Dermatology Times - November 12th, 2024 [November 12th, 2024]
- Memorial Health System is re-opening of Department of Dermatology - Parkersburg News - October 26th, 2024 [October 26th, 2024]
- Available Therapeutics and Upcoming Advancements in Atopic Dermatitis and Prurigo Nodularis - Dermatology Times - October 26th, 2024 [October 26th, 2024]
- Sun Pharma Announces Multiple Data Presentations Highlighting its Dermatology Portfolio to be Featured at the 2024 Fall Clinical Dermatology... - October 26th, 2024 [October 26th, 2024]
- What To Look Forward To at the Fall Clinical Dermatology Conference, with Raj Chovatiya, MD, PhD - MD Magazine - October 26th, 2024 [October 26th, 2024]
- Navigating Complexities and Unmet Needs of Chronic Hand Eczema - Dermatology Times - October 26th, 2024 [October 26th, 2024]
- Schweiger Dermatology Group Expands in Florida with the Acquisition of ClearlyDerm, Adding 5 New Offices in South Florida - PR Newswire - October 26th, 2024 [October 26th, 2024]
- Leo Pharma tells doctors to 'Talk to the Hand' in new dermatology campaign - FiercePharma - October 26th, 2024 [October 26th, 2024]
- Dermatology Partners To Expand Maryland Presence With New Westminster Clinic, Hosts Free Skin Cancer Screenings For Veterans On November 11 - citybiz - October 26th, 2024 [October 26th, 2024]
- Peter Lio, MD: The Latest Perspectives on Pathophysiology and Treatment of Eczema - Dermatology Times - October 26th, 2024 [October 26th, 2024]
- Verrica Pharmaceuticals Announces Acceptance of Two Abstracts Featuring Positive Preliminary Topline Results of VP-315 for the Treatment of Basal Cell... - October 26th, 2024 [October 26th, 2024]
- Dermatology Patients Taking Biologics are Wary About Most Vaccines - Medpage Today - October 13th, 2024 [October 13th, 2024]
- Safe and Effective: Upadacitinib Shows Promise in PN Treatment - Dermatology Times - October 13th, 2024 [October 13th, 2024]
- SPONSORED: First Care, Heartland Dermatology team up again for free health screening event - Hays Post - October 13th, 2024 [October 13th, 2024]
- Global Dermatology Drugs Market to Worth Over US$ 50.42 Billion By 2032 | Astute Analytica - GlobeNewswire - October 13th, 2024 [October 13th, 2024]
- Working to Improve Mental Health - Dermatology Times - October 13th, 2024 [October 13th, 2024]
- Bimekizumab Demonstrates Safety and Efficacy in Elderly Patients with Psoriasis - Dermatology Times - October 13th, 2024 [October 13th, 2024]
- Analyzing Efficacy and Safety in Diverse Clinical Trials: New Roflumilast Data - Dermatology Times - October 2nd, 2024 [October 2nd, 2024]
- UCB at EADV 2024: committed to advancing care in immuno-dermatology - UCB - October 2nd, 2024 [October 2nd, 2024]
- Positive Results Reported in Roflumilast 0.15% for AD Across Diverse Populations - Dermatology Times - October 2nd, 2024 [October 2nd, 2024]
- Expert Insights Into Handling Treatment Challenges and Site-Specific Concerns in Vitiligo Management - Dermatology Times - October 2nd, 2024 [October 2nd, 2024]
- Dermatology Excimer Laser Market is expected to Double Its Size - openPR - October 2nd, 2024 [October 2nd, 2024]
- InflaRx Presents Post Hoc Analysis of SHINE Trial of Vilobelimab in Hidradenitis Suppurativa at the 2024 European Academy of Dermatology and... - October 2nd, 2024 [October 2nd, 2024]
- Discussing Unmet Needs Among Patients in Dermatology, with Matthew Zirwas, MD - MD Magazine - September 23rd, 2024 [September 23rd, 2024]
- Organon Moves Into Branded Dermatology With Dermavant Takeout - Scrip - September 23rd, 2024 [September 23rd, 2024]
- Dermatology Research Team Investigating the Most Common Disease Youve Never Heard About - University of Miami - September 23rd, 2024 [September 23rd, 2024]
- Astria Therapeutics to Present at Upcoming European Academy of Dermatology and Venerology Congress - Business Wire - September 23rd, 2024 [September 23rd, 2024]
- Hensin Tsao, MD, PhD: TIL Therapy and Neoadjuvant Treatment for Pigmented Lesions - Dermatology Times - September 23rd, 2024 [September 23rd, 2024]
- Derm In The News: September 8-14 - Dermatology Times - September 15th, 2024 [September 15th, 2024]
- April Armstrong, MD, MPH, Shares Insights on the NPF's Psoriasis Health Indicator Report - Dermatology Times - September 15th, 2024 [September 15th, 2024]
- Nearly half of FDA-authorized AI tools may be ineffective - Dermatology Times - September 15th, 2024 [September 15th, 2024]
- Dermatology Diagnostic Devices And Therapeutics Market - openPR - September 15th, 2024 [September 15th, 2024]
- Industry Deep Dive: Dermatology Devices Market Size, Share, and Growth Forecast with Emerging Trends through 2032 - openPR - September 15th, 2024 [September 15th, 2024]
- SPROUT Trial Highlights Benefits of Apremilast for Pediatric Psoriasis - Dermatology Times - September 15th, 2024 [September 15th, 2024]
- Veterinary Dermatology Drugs Market Global Latest Trends and Insights 2024 to 2031 - openPR - September 15th, 2024 [September 15th, 2024]
- Championing equity in skin of color dermatology - Fierce healthcare - August 5th, 2024 [August 5th, 2024]
- Derm In The News: July 28-August 3 - Dermatology Times - August 5th, 2024 [August 5th, 2024]
- Interview Intersection: Expert Interviews From July 2024 - Dermatology Times - August 5th, 2024 [August 5th, 2024]
- Generation Z, Millennials Exhibit Similar Subjective Perception of Atopic Dermatitis Disease Severity - Dermatology Times - August 5th, 2024 [August 5th, 2024]
- Long-Term Efficacy and Insights from POETYK PSO-1 Studies: Implications for Psoriasis Treatment - Dermatology Times - August 5th, 2024 [August 5th, 2024]
- Laurel Dermatology emphasizes the importance of sunscreen - WDAM - July 26th, 2024 [July 26th, 2024]
- The Interplay Between Sleep Disorders and Dermatology - Dermatology Times - July 26th, 2024 [July 26th, 2024]
- Latex Gloves and the Americans With Disabilities Act - Dermatology Times - July 26th, 2024 [July 26th, 2024]
- Advanced Practice Providers Share Insights at the 2024 Society for Pediatric Dermatology Annual Meeting - Dermatology Times - July 26th, 2024 [July 26th, 2024]
- Almiralls H1 2024 Results: Almirall Delivers Strong Performance in the First Half of 2024, Achieving Net Sales Growth of 6.7% Driven by Its European... - July 26th, 2024 [July 26th, 2024]
- Arcutis Submits sNDA for Roflumilast Foam to FDA for Scalp and Body Psoriasis - Dermatology Times - July 26th, 2024 [July 26th, 2024]
- Appier and SkinX Thailand Partner to Revolutionise Dermatology Services with AI - SME Magazine - July 26th, 2024 [July 26th, 2024]
- Diagnostic dermatology market to be valued at $43.4b by 2034 - Healthcare Asia - July 26th, 2024 [July 26th, 2024]
- FDNY Partners with American Academy of Dermatology to Provide Free Skin Cancer Checks - nyc.gov - June 1st, 2024 [June 1st, 2024]
- Day 1 Recap: 2024 Fall Clinical Dermatology Conference for PAs and NPs - Dermatology Times - June 1st, 2024 [June 1st, 2024]
- Dermatology's Rosanne Paul discusses safety of foot peels - The Daily | Case Western Reserve University - June 1st, 2024 [June 1st, 2024]
- Sneak Peek: 2024 Fall Clinical Dermatology Conference for PAs and NPs - Dermatology Times - June 1st, 2024 [June 1st, 2024]
- New Dermatology Center to Open at The Grand Resort's Med Spa - businessjournaldaily.com - June 1st, 2024 [June 1st, 2024]
- Dermatology Care of Alabama goes the extra mile to give the best care - Hoover Sun - June 1st, 2024 [June 1st, 2024]
- QUIZ RECAP: Treatment and Management of Skin Cancer - Dermatology Times - June 1st, 2024 [June 1st, 2024]
- What to Know About Peptides, the Retinol Alternative Dermatologists Love | SELF - Self - June 1st, 2024 [June 1st, 2024]
- Reviewing Common and Prevalent Dermatoses in AAPI Patients - Dermatology Times - June 1st, 2024 [June 1st, 2024]
- Dermatologists Advise Against Taking Bite Of Facial Cream - The Onion - June 1st, 2024 [June 1st, 2024]
- Prescription Dermatology Therapeutics Market Drivers And Restraints Identified Through SWOT Analysis 2030 - openPR - June 1st, 2024 [June 1st, 2024]
- Derm In The News: May 19-25 - Dermatology Times - June 1st, 2024 [June 1st, 2024]
- What Gen Z Should Know About Sunscreen to Help Protect From Skin Cancer - The New York Times - June 1st, 2024 [June 1st, 2024]
- American Academy of Dermatology Association Statement on Reports on Counterfeit Injectables - Newswise - April 15th, 2024 [April 15th, 2024]
- Surface Area of IL-23's Epitope Influences Short- and Long-Term Responses for IL-23 Inhibitors in Plaque Psoriasis - Dermatology Times - April 15th, 2024 [April 15th, 2024]
- Atopic Dermatitis (Eczema): 5 Top Self-Care Tips - Everyday Health - April 15th, 2024 [April 15th, 2024]
- Derm In The News: April 7-13 - Dermatology Times - April 15th, 2024 [April 15th, 2024]