scholarly journals Immune Checkpoint Blockade in Advanced Cutaneous Squamous Cell Carcinoma: What Do We Currently Know in 2020?

2020 ◽  
Vol 21 (23) ◽  
pp. 9300
Author(s):  
Anja Wessely ◽  
Theresa Steeb ◽  
Ulrike Leiter ◽  
Claus Garbe ◽  
Carola Berking ◽  
...  

Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer that predominantly arises in chronically sun-damaged skin. Immunosuppression, genetic disorders such as xeroderma pigmentosum (XP), exposure to certain drugs and environmental noxae have been identified as major risk factors. Surgical removal of cSCC is the therapy of choice and mostly curative in early stages. However, a minority of patients develop locally advanced tumors or distant metastases that are still challenging to treat. Immune checkpoint blockade (ICB) targeting CTLA-4, PD-L1 and PD-1 has tremendously changed the field of oncological therapy and especially the treatment of skin cancers as tumors with a high mutational burden. In this review, we focus on the differences between cSCC and cutaneous melanoma (CM) and their implications on therapy, summarize the current evidence on ICB for the treatment of advanced cSCC and discuss the chances and pitfalls of this therapy option for this cancer entity. Furthermore, we focus on special subgroups of interest such as organ transplant recipients, patients with hematologic malignancies, XP and field cancerization.

Molecules ◽  
2021 ◽  
Vol 26 (5) ◽  
pp. 1392
Author(s):  
Hong Yuan ◽  
Jing Liu ◽  
Jun Zhang

In addition to surgery, chemotherapy, radiotherapy, and targeted therapy, immunotherapy has emerged as a standard pillar of cancer treatment. Immune checkpoint inhibitors (ICIs) such as targeting programmed death-1/programmed death ligand 1 (PD-1/PD-L1) and cytotoxic T lymphocyte antigen 4 (CTLA-4) have been integrated into standard-of-care regimens for patients with advanced lung squamous cell carcinoma (LUSC), who were previously limited by the lack of treatment options. Atezolizumab, durvalumab, nivolumab, and pembrolizumab are all currently used as part of standard-of-care treatment for different stages of lung cancer. Recent successes and failures of immune checkpoint blockade-based combination therapies have provided significant insights into implementing combination strategies in LUSC. Therefore, there is an urgent need to correctly select patients who are more likely to respond to immunotherapy and understand the mechanisms of primary or acquired resistance. In this review, we aim at summarizing the emerging clinical data on the promise and challenge of ICIs, discussing the unmet need of potential biomarkers for predicting response or resistance to immunotherapy, and providing an overview of the current immune landscape and future directions in advanced LUSC.


2021 ◽  
Vol 11 (S2) ◽  
pp. e2021170S
Author(s):  
Paolo Bossi ◽  
Luigi Lorini

Cutaneous squamous cell carcinoma (cSCC) may develop in patients with dysregulated immune activation (pre-existing autoimmune diseases or immunosuppression due to hematopoietic/solid organ transplant recipients), patients with a compromised immune function (long-term immunosuppression), and patients carrying chronic viral infections, or those affected by lymphoproliferative diseases. It should be also considered that patients presenting with immunosuppression have a high incidence of cSCC (65–250-times higher than general population), highlighting the central role played by the immune system in the development of cSCC. All these cases must be considered as “special populations” for treatment with immune checkpoint inhibitors (ICIs), as the safety and activity of these drugs have not been studied on these specific cases, since these patients were excluded from clinical trials leading to approval of ICIs. It is therefore important to gain as much information as possible from the analysis of real-life data, to derive an indication to be adopted in everyday clinical setting.  Moreover, therapeutic alternatives other than ICIs are scarce, mainly consisting in chemotherapy and anti-EGFR agents, whose activity is lower than immunotherapy and whose toxicity (particularly with chemotherapy) are not sustainable by this frail population. Here, we describe the current evidence of treatment with ICIs in special populations and conclude that it is necessary to find a balance between treatment risks (toxicities) and benefits (efficacy), as well as engaging a multidisciplinary team of experts to thoroughly manage and treat these patients.


2018 ◽  
Vol 72 (4) ◽  
pp. 1-5 ◽  
Author(s):  
Krzysztof Przybylski ◽  
Ewa Majchrzak ◽  
Liucija Weselik ◽  
Wojciech Golusiński

Leczenie chorych na raka płaskonabłonkowego głowy i szyi jest istotnym problemem. Obserwuje się wzrost zachorowalności na nowotwory złośliwe tego regionu. Chirurgia, radioterapia oraz chemioterapia często nie są wystarczającymi metodami leczenia. Dokładna analiza procesów zachodzących w mikrośrodowisku guza pozwoliła na wyodrębnienie trzech etapów składających się na reakcję organizmu człowieka na wrogie antygeny, jakimi są antygeny nowotworowe. Poznanie tych mechanizmów skutkowało wprowadzeniem nowego terminu immunoonkologia. Jest to dziedzina leczenia nowotworów skupiająca się na wykorzystaniu układu immunologicznego pacjenta w celu zwalczania choroby. Immunoterapia u chorych na raka przyniosła pozytywne efekty. Wykorzystanie inhibitorów immunologicznych punktów kontroli, jak przeciwciała monoklonalne przeciwko receptorowi CTLA – 4 oraz PD – 1 umożliwiło modulację funkcji limfocytów T w konsekwencji znosząc immunosupresję w mikrośrodowisku guza. Przeprowadzono badania kliniczne z zastosowaniem nivolumabu oraz ipilimumabu, które potwierdziły ich przydatność kliniczną. Zatwierdzenie przez FDA nivolumabu w leczeniu nawrotowego i przerzutowego raka płaskonabłonkowego głowy i szyi wydłużyło całkowity czas przeżycia chorych oraz czas przeżycia wolny od choroby. Dane statystyczne wskazują na przewagę immunoterapii nad innymi metodami leczenia w zaawansowanym stadium choroby nowotworowej. Celem pracy jest omówienie podstawowych zagadnień związanych z immunoterapią, w szczególności immunoterapią u chorych na raka płaskonabłonkowego głowy i szyi.


Oral Oncology ◽  
2020 ◽  
Vol 105 ◽  
pp. 104676 ◽  
Author(s):  
Alec J. Kacew ◽  
Ethan J. Harris ◽  
Jochen H. Lorch ◽  
Jonathan D. Schoenfeld ◽  
Danielle N. Margalit ◽  
...  

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