scholarly journals Cancer Immunotherapy Biomarkers of Response and Toxicity; Current Limitations and Future Promise

Author(s):  
Brian Richard Healey Bird ◽  
Ken Nally ◽  
Karine Ronan ◽  
Gerard Clarke ◽  
Sylvie Amu ◽  
...  

Immune Checkpoint Inhibitors are monoclonal antibodies that are used to treat over one in three cancer patients. While they have changed the natural history of disease, prolonging life and preserving quality of life, they are highly active in less than 40% of patients, even in the most responsive malignancies such as melanoma, and cause significant autoimmune side effects. Licenced biomarkers include tumour Programmed Death Ligand 1 expression by immunohistochemistry, microsatellite instability, and Tumour Mutational Burden, none of which are particularly sensitive or specific. Emerging tumour and immune tissue biomarkers such as novel immunohistochemistry scores, tumour, stromal and immune cell gene expression profiling, and liquid biomarkers such as systemic inflammatory markers, kynurenine/tryptophan ratio, circulating immune cells, cytokines and DNA are discussed in this review. We also examine the influence of the faecal microbiome on treatment outcome and its use as a biomarker of response and toxicity.

Diagnostics ◽  
2022 ◽  
Vol 12 (1) ◽  
pp. 124
Author(s):  
Brian Healey Bird ◽  
Ken Nally ◽  
Karine Ronan ◽  
Gerard Clarke ◽  
Sylvie Amu ◽  
...  

Immune checkpoint inhibitors are monoclonal antibodies that are used to treat over one in three cancer patients. While they have changed the natural history of disease, prolonging life and preserving quality of life, they are highly active in less than 40% of patients, even in the most responsive malignancies such as melanoma, and cause significant autoimmune side effects. Licenced biomarkers include tumour Programmed Death Ligand 1 expression by immunohistochemistry, microsatellite instability, and tumour mutational burden, none of which are particularly sensitive or specific. Emerging tumour and immune tissue biomarkers such as novel immunohistochemistry scores, tumour, stromal and immune cell gene expression profiling, and liquid biomarkers such as systemic inflammatory markers, kynurenine/tryptophan ratio, circulating immune cells, cytokines and DNA are discussed in this review. We also examine the influence of the faecal microbiome on treatment outcome and its use as a biomarker of response and toxicity.


Cell ◽  
2018 ◽  
Vol 175 (6) ◽  
pp. 1701-1715.e16 ◽  
Author(s):  
Benjamin J. Schmiedel ◽  
Divya Singh ◽  
Ariel Madrigal ◽  
Alan G. Valdovino-Gonzalez ◽  
Brandie M. White ◽  
...  

Cells ◽  
2019 ◽  
Vol 8 (8) ◽  
pp. 809 ◽  
Author(s):  
Kloten ◽  
Lampignano ◽  
Krahn ◽  
Schlange

Over the last decade, the immune checkpoint blockade targeting the programmed death protein 1 (PD-1)/programmed death ligand 1 (PD-L1) axis has improved progression-free and overall survival of advanced non-small cell lung cancer (NSCLC) patients. PD-L1 tumor expression, along with tumor mutational burden, is currently being explored as a predictive biomarker for responses to immune checkpoint inhibitors (ICIs). However, lung cancer patients may have insufficient tumor tissue samples and the high bleeding risk often prevents additional biopsies and, as a consequence, immunohistological evaluation of PD-L1 expression. In addition, PD-L1 shows a dynamic expression profile and can be influenced by intratumoral heterogeneity as well as the immune cell infiltrate in the tumor and its microenvironment, influencing the response rate to PD-1/PD-L1 axis ICIs. Therefore, to identify subgroups of patients with advanced NSCLC that will most likely benefit from ICI therapies, molecular characterization of PD-L1 expression in circulating tumor cells (CTCs) might be supportive. In this review, we highlight the use of CTCs as a complementary diagnostic tool for PD-L1 expression analysis in advanced NSCLC patients. In addition, we examine technical issues of PD-L1 measurement in tissue as well as in CTCs.


2020 ◽  
Vol 8 ◽  
pp. 2050313X1989770 ◽  
Author(s):  
Anastasia Politi ◽  
Dimas Angelos ◽  
Davide Mauri ◽  
George Zarkavelis ◽  
George Pentheroudakis

Immune checkpoint inhibitors, such as anti-cytotoxic T-lymphocyte–associated antigen-4 and anti-programmed death-1, are a type of cancer immunotherapy approved for late-stage malignancy treatment. However, such therapies often induce immune-related adverse events. During anti-programmed death-1 blockade therapy, the most commonly reported adverse effects are skin toxicities, such as psoriasis—a chronic immune-mediated inflammatory disorder affecting the skin. We present the clinical characteristics of flared psoriasis in one patient under anti-programmed death-1 therapy who was diagnosed with T2N2M0/IIIB squamous lung carcinoma with a history of psoriasis for the past 5 years, exacerbated after the first cycle of nivolumab. After the third cycle, the extensive skin plaques necessitated treatment cessation. Following the discontinuation of anti-programmed death-1 treatment, skin lesions were treated locally. Possibly, anti-programmed death-1 immunotherapy can trigger immune-mediated diseases, such as psoriasis. Physicians should be alert to immune-related adverse events. Continuation or permanent cessation of treatment depends on the severity and reversibility of immune-related adverse events.


Urban History ◽  
1980 ◽  
Vol 7 ◽  
pp. 53-62 ◽  
Author(s):  
Bill Luckin

Now that the debate about the standard of living during the first half of the nineteenth century appears to have entered a relatively quiescent phase, historians have begun to turn their attention towards the more elusive concept of the quality of life. The incidence of fatal and non-fatal disease is clearly central to research of this type and so, too, is a delineation of the physical context in which infections have flourished and in which those who have been afflicted by them have lived. Although there has been a tendency to underestimate the ferocity of epidemics in rural areas in the period after about 1750, historians working on disease in the modern period are inevitably most usually concerned with processes which are specifically urban in character. And urban historians, especially those interested in such topics as the development of utilities, the growth of administrative bureau-cracies or the spatial segregation and different life experiences of the classes, can undoubtedly benefit from a knowledge of patterns of infection in the past.


2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 18538-18538
Author(s):  
L. Curreli ◽  
A. D. Palmas ◽  
G. Latte ◽  
A. Murgia ◽  
A. Gabbas

18538 Background: Oral cavity avascular bone necrosis (ABN) has been recently reported as an emerging serious complication in pts receiving BP for the treatment of hypercalcemia related to MM or metastatic solid tumors. Methods: We report the cases of 6 pts with MM treated initially with pamidronate and later with zoledronic acid (ZA). Results: Pts characteristics : M/F 3/3; mean age 58.4 (46–78); 4 IgG κ,1 γ and 1 κ MM; 5 St IIIA and 1 IIIB; mean history of disease 61.3 mo. (23–103); 5 pts had a relapsing MM refractory to several lines of therapy but 1 pt had received only high dose dexametazone (D); 2 pts had received autologous stem cell transplantation and 1 pt allogenic bone marrow transplantation; mean n.° of BP doses was 41.3 (17–81). At the time of ABN onset all pts were receiving ZA along with, respectively: D (2 pts); cyclophosphamide plus D (1 pt), bortezomib plus D (2 pts) and oral melphalan (1 pt). ABN was localized in 2 pts at alveolar bone of the right maxilla and presented as an inflammation of the gum, followed by a painful bone exposure. In the other 4 pts ABN was localized at mandible and presented as dental abscesses followed in 2/4 pts by cutaneous fistulization. Treatment has included in all pts discontinuation of ZA, antibiotics, chlorhexidine mouthwashes, pain control, minor regional débridement, and bone trimming. In 1 pt a more aggressive surgical approach was attempted at an other Institution and postoperative course was complicated by massive haemorrhage and complete loss of chewing. Four pts dead with progressive disease with a mean overall survival after ABN presentation of 6 mo.; 2 pts are alive after 3 and 4 mo. after ABN presentation; however in all pts ABN significantly worsened quality of life. Conclusions: Oral cavity ABN is a severe complication in refractory MM pts receiving BP. Mechanisms of action of BP that determine a reduction in osteoclastic activity and an accumulation of nonvital osteocytes with microfractures of old mineral matrix appear to play an important role. However other causes may be involved as a long history of disease; an uncontrolled progressive disease; type and doses of previous and present therapies, primarily steroids; status of oral cavity and teeth of pts and possibly the n.° of doses of BP. No significant financial relationships to disclose.


Sign in / Sign up

Export Citation Format

Share Document