Biology subjects

TAN, D. S. W.

Publications and source records attributed to TAN, D. S. W..

2 recordsLinked to original sources

bioRxiv2020

Bystander CD4+ T cells infiltrate human tumors and are phenotypically distinct

Tumor-specific T cells likely underpin effective immune checkpoint-blockade therapies. Yet, most studies focus on Treg cells and CD8+ tumor-infiltrating lymphocytes (TILs). Here we study CD4+ TILs in human lung and colorectal cancers and observe that non-Treg CD4+ TILs average more than 70% of total CD4+ TILs in both cancer types. Leveraging high dimensional analyses including mass cytometry and single-cell sequencing, we reveal that CD4+ TILs are heterogeneous at both gene and protein levels, within each tumor and across patients. Consistently, we find different subsets of CD4+ TILs showing characteristics of effectors, tissue resident memory (Trm) or exhausted cells (expressing PD-1, CTLA-4 and CD39). In both cancer types, the frequencies of CD39- non-Treg CD4+ TILs strongly correlate with frequencies of CD39- CD8+ TILs, which we and others have previously shown to be enriched for cells specific for cancer-unrelated antigens (bystanders). Ex-vivo, we demonstrate that CD39- CD4+ TILs can be specific for cancer unrelated antigens, such as HCMV epitopes. Overall, our findings highlight that CD4+ TILs cells are not necessarily tumor-specific and suggest measuring CD39 expression as a straightforward way to quantify or isolate bystander CD4+ T cells. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=158 SRC="FIGDIR/small/204172v1_ufig1.gif" ALT="Figure 1"> View larger version (38K): org.highwire.dtl.DTLVardef@13de05org.highwire.dtl.DTLVardef@553e34org.highwire.dtl.DTLVardef@66e9f1org.highwire.dtl.DTLVardef@8903ca_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

bioRxiv2019

Partial absence of PD-1 expression by tumor-specific CD8+ T cells in EBV-driven lymphoepithelioma-like carcinoma: a case report

Lymphoepithelioma-like carcinoma (LELC) is an uncommon lung cancer, typically observed in young, non-smoking Asian populations. LELC is associated with Epstein-Barr virus (EBV) infection of lung tumor cells of epithelial origin, suggesting a carcinogenic role of EBV as observed in nasopharyngeal carcinoma (NPC). Here, we studied the antigen specificity and phenotype of CD8+ tumor infiltrating lymphocytes (TILs) in one LELC patient positive for EBV infection in lung tumor cells. Using MHC class I tetramers, we detected two populations of EBV-specific CD8+ TILs, which can be considered as tumor-specific CD8+ T cells, in the tumor of this patient. Transcriptomic analyses of these two populations reveal their distinct exhausted profiles and polyclonal TCR repertoire. High dimensional analyses at single cell level using mass cytometry showed showed that populations of tumor specific CD8+ TILs are phenotypically heterogeneous, although they consistently express CD39. Unexpectedly, although the LELC tumor cells expressed abundant PD-L1, these tumor-specific CD8+ TILs mostly did not express PD-1, suggesting that anti-PD1/PD-L1 immunotherapy may not be an appropriate strategy for disinhibiting EBV-specific cells for the treatment of LELC patients. These results might also help to explain low rates of checkpoint blockade immunotherapy response for NPC, despite the antigenicity of EBV for both tumor types.

cancer biology↗