Decreased cytotoxic T cells and TCR clonality in organ transplant recipients with squamous cell carcinoma

T-cell landscape differences between cutaneous squamous cell carcinoma (cSCC) tumors in immune competent (SCC in IC) and immunocompromised organ transplant recipients (TSCC in OTR) are unclear. We developed an analytical method to define tumor infiltrating lymphocyte (TIL) phenotype in cSCC from imm...

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Published inNPJ precision oncology Vol. 4; no. 1; p. 13
Main Authors Frazzette, Nicholas, Khodadadi-Jamayran, Alireza, Doudican, Nicole, Santana, Alexis, Felsen, Diane, Pavlick, Anna C., Tsirigos, Aristotelis, Carucci, John A.
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group UK 03.06.2020
Nature Publishing Group
Subjects
631/67/1813/1352
631/67/327
631/67/580
692/699/67/1813/1352
Antigens
Cancer Research
Cytotoxicity
Gene expression
Gene Therapy
Human Genetics
Internal Medicine
Lymphocytes
Medicine
Medicine & Public Health
Oncology
Patients
Skin cancer
Squamous cell carcinoma
Transplants & implants
Tumors
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Abstract T-cell landscape differences between cutaneous squamous cell carcinoma (cSCC) tumors in immune competent (SCC in IC) and immunocompromised organ transplant recipients (TSCC in OTR) are unclear. We developed an analytical method to define tumor infiltrating lymphocyte (TIL) phenotype in cSCC from immune competent and immune suppressed patients using single-cell TCR sequencing and gene expression data. TSCC exhibits reduced proportions of cytotoxic and naïve TILs and similar numbers of regulatory TILs. Fewer, more heterogeneous TCR clonotypes are observed in TIL from OTR. Most TCR sequences for top ten clonotypes correspond to known antigens, while 24% correspond to putative neoantigens. OTR show increased cSCC events over 12 months possibly due to reduced cytotoxic T-cells. Our novel method of barcoding CD8+ T-cells is the first providing gene expression and TCR sequences in cSCC. Knowledge regarding putative antigens recognized by TCRs with phenotypic function of T-cells bearing those TCRs could facilitate personalized cSCC treatments.
AbstractList T-cell landscape differences between cutaneous squamous cell carcinoma (cSCC) tumors in immune competent (SCC in IC) and immunocompromised organ transplant recipients (TSCC in OTR) are unclear. We developed an analytical method to define tumor infiltrating lymphocyte (TIL) phenotype in cSCC from immune competent and immune suppressed patients using single-cell TCR sequencing and gene expression data. TSCC exhibits reduced proportions of cytotoxic and naïve TILs and similar numbers of regulatory TILs. Fewer, more heterogeneous TCR clonotypes are observed in TIL from OTR. Most TCR sequences for top ten clonotypes correspond to known antigens, while 24% correspond to putative neoantigens. OTR show increased cSCC events over 12 months possibly due to reduced cytotoxic T-cells. Our novel method of barcoding CD8+ T-cells is the first providing gene expression and TCR sequences in cSCC. Knowledge regarding putative antigens recognized by TCRs with phenotypic function of T-cells bearing those TCRs could facilitate personalized cSCC treatments.
Abstract T-cell landscape differences between cutaneous squamous cell carcinoma (cSCC) tumors in immune competent (SCC in IC) and immunocompromised organ transplant recipients (TSCC in OTR) are unclear. We developed an analytical method to define tumor infiltrating lymphocyte (TIL) phenotype in cSCC from immune competent and immune suppressed patients using single-cell TCR sequencing and gene expression data. TSCC exhibits reduced proportions of cytotoxic and naïve TILs and similar numbers of regulatory TILs. Fewer, more heterogeneous TCR clonotypes are observed in TIL from OTR. Most TCR sequences for top ten clonotypes correspond to known antigens, while 24% correspond to putative neoantigens. OTR show increased cSCC events over 12 months possibly due to reduced cytotoxic T-cells. Our novel method of barcoding CD8+ T-cells is the first providing gene expression and TCR sequences in cSCC. Knowledge regarding putative antigens recognized by TCRs with phenotypic function of T-cells bearing those TCRs could facilitate personalized cSCC treatments.
ArticleNumber 13
Author Felsen, Diane
Carucci, John A.
Frazzette, Nicholas
Pavlick, Anna C.
Tsirigos, Aristotelis
Doudican, Nicole
Santana, Alexis
Khodadadi-Jamayran, Alireza
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Snippet T-cell landscape differences between cutaneous squamous cell carcinoma (cSCC) tumors in immune competent (SCC in IC) and immunocompromised organ transplant...
Abstract T-cell landscape differences between cutaneous squamous cell carcinoma (cSCC) tumors in immune competent (SCC in IC) and immunocompromised organ...
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SubjectTerms 631/67/1813/1352
631/67/327
631/67/580
692/699/67/1813/1352
Antigens
Cancer Research
Cytotoxicity
Gene expression
Gene Therapy
Human Genetics
Internal Medicine
Lymphocytes
Medicine
Medicine & Public Health
Oncology
Patients
Skin cancer
Squamous cell carcinoma
Transplants & implants
Tumors
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Title Decreased cytotoxic T cells and TCR clonality in organ transplant recipients with squamous cell carcinoma
URI https://link.springer.com/article/10.1038/s41698-020-0119-9
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