Tumor Characteristics in Patients With Paraneoplastic Neurological Syndromes (PNS)

Study Overview
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Brief Summary
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Paraneoplastic neurological syndromes (PNS) are immune-mediated complications of cancer that can affect any part of the central or peripheral nervous system. PNS occurs at the intersection between immune system and the tumor, where a combination of genetical and environmental factors may play a role. Mechanisms leading to immune tolerance breakdown and autoimmunity in PNS remain largely unknown, and this reflects in an unsatisfactory repertoire of treatments available. Moreover, a better understanding of the biological mechanisms underlying PNS would allow a more precise identification of the modalities that permit PNS patients to have a better oncological prognosis than cancer patient without PNS, with obvious repercussions in clinical oncology. To this effect, an extremely innovative approach involves directly exploring the tumoral tissue of patients suffering from specific PNS via genomic and transcriptomic analysis. The study team hypothesizes that antigen ectopic expression by tumour cells may contribute to the generation of PNS. In the present study, the investigators will analyze the salient features of tumors associated with PNS, namely the histological and immune cells infiltrate characteristics, their transcriptomic profile, and mutational status of involved antigens.

Official Title
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Genomic Profile and Tumor Immune Attack in Paraneoplastic Neurological Syndromes (PNS)

Conditions
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Cancer, Paraneoplastic Syndromes, Neurologic Disorder, Immune System and Related Disorders, Tumor Genetics

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: presence of well characterized antibodies in serum or cerebrospinal fluid; histologically proven cancer with available tumour sample; Paraneoplastic neurological syndrome (PNS) diagnosis according to the international guidelines; Age: at least 18 years old. Exclusion Criteria: Absence of complete clinicopathological data

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Cancer patients with Paraneoplastic neurological syndromes<br>Cancer patients with Paraneoplastic neurological syndromes presenting various autoimmune anomalies: Anti-Hu also known as anti-Neuron specific cell Nuclear Antibodies (anti-ANNA1) (350 patients), uncommon form of brain inflammation associated with an underlying cancer anti-Yo (130 patients), antibody associated with paraneoplastic cerebellar degeneration anti-Ma2 (50 patients), antibody associated with paraneoplastic encephalitis anti-N-methyl-d-aspartate (NMDA) Receptor (350 patients), autoimmune disorder in which antibodies attack N-methyl-D-aspartate-type glutamate receptors anti-gamma-aminobutyric acid-B (GABAb) receptor (35 patients), autoimmune disorder in which antibodies attack gamma-aminobutyric acid-B receptors anti-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor (15 patients), autoimmune disorder in which antibodies attack alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors without antibodies (50 patients). | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of mutations in cancer genes coding for onconeural proteins and inflammatory response mediators. | Genetic alterations in tumors associated with Paraneoplastic neurological syndromes (PNS) | 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of different immune cells in the tumor's immune infiltrate | Histological immune infiltrate characteristics | 36 months |