High‐throughput sequencing of T‐cell receptors reveals a homogeneous repertoire of tumour‐infiltrating lymphocytes in ovarian cancer

Abstract

The cellular adaptive immune system mounts a response to many solid tumors mediated by tumor infiltrating T lymphocytes (TILs). Basic measurements of these TILs, including total count, show promise as prognostic markers for a variety of cancers, including ovarian and colorectal. In addition, recent therapeutic advances are thought to exploit this immune response to effectively fight melanoma with promising studies showing efficacy in additional cancers. However, many of the basic properties of TILs are poorly understood including specificity, clonality, and spatial heterogeneity of the T cell response. We utilize deep sequencing of rearranged T-cell receptor beta (TCRB) genes to characterize the basic properties of TILs in ovarian carcinoma. Due to somatic rearrangement during T cell development, the TCR beta chain sequence serves as a molecular tag for each T cell clone. Using these sequence tags, we assess similarities and differences between infiltrating T cells in discretely sampled sections of large tumors and compare to T cells from peripheral blood. Within the limits of sensitivity of our assay, the TIL repertoires show strong similarity throughout each tumor and are distinct from the circulating T cell repertoire. We conclude that the cellular adaptive immune response within ovarian carcinomas is spatially homogeneous and distinct from the T cell compartment of peripheral blood.

T cell receptor richness in peripheral blood increases after cetuximab therapy and correlates with therapeutic response

“…So far, differences in PBL and in TIL have been observed. 23 Still, factors that influence the landscape of TIL are poorly understood.…”

High-throughput T cell receptor sequencing reveals distinct repertoires between tumor and adjacent non-tumor tissues in HBV-associated HCC

“…These values are smaller than the degree of tumor and normal tissue overlap in ESCC, which accounted for approximately 25% of samples, but similar to the degree of tumor and adjacent mucosal tissue overlap in colorectal tumors, which ranged from 0.2 to 38%. 29,30 This difference might be related to the different starting materials and approaches for TCR profiling. Although starting from genomic DNA and multiplexed PCR strategies is relatively easier for performing, these techniques are associated with significant bias.…”

A high density of tertiary lymphoid structure B cells in lung tumors is associated with increased CD4+T cell receptor repertoire clonality

“…[27][28][29] Among the different T cell subsets, both the intratumoral and inter-compartmental heterogeneity of the TCR repertoire has been reported in studies in many types of cancer including colorectal, renal cell, and ovarian cancer. 23,30,31 Even within CD8 C T cells, subsets with expression of different surface markers have revealed differences in oligoclonal expansion in TCRb clonotypes. 32 These results underlie the importance of appropriate characterization of the activation and infiltration status within tumor or normal compartments with a mixed population of T cell subsets that differ in complexity and diversity.…”

“…22 TCR and BCR repertoire technology can provide a robust characterization of the global receptor repertoire of particular lymphocyte populations, though within both the peripheral and diseaseaffected compartments, there is a mixed population of T cells that can differ by clonotype contribution, cell subtypes, and sensitivities to therapies. 2,3,23 Further, the frequencies of monoclonal and oligoclonal TCR Vb families have been shown to significantly differ between CD4…”