scholarly journals Contribution of resident and circulating precursors to tumor-infiltrating CD8+ T cell populations in lung cancer

2021 ◽  
Vol 6 (55) ◽  
pp. eabd5778
Author(s):  
Paul Gueguen ◽  
Christina Metoikidou ◽  
Thomas Dupic ◽  
Myriam Lawand ◽  
Christel Goudot ◽  
...  
Keyword(s):  
Lung Cancer ◽  
T Cell ◽  
Functional Organization ◽  
Tumor Infiltrating Lymphocytes ◽  
Cell Receptor ◽  
Transitional State ◽  
Differentiated Cells ◽  
Primary Nsclc ◽  
Favorable Prognostic Factor ◽  
Infiltrating Lymphocytes

Tumor-infiltrating lymphocytes (TILs), in general, and especially CD8+ TILs, represent a favorable prognostic factor in non–small cell lung cancer (NSCLC). The tissue origin, regenerative capacities, and differentiation pathways of TIL subpopulations remain poorly understood. Using a combination of single-cell RNA and T cell receptor (TCR) sequencing, we investigate the functional organization of TIL populations in primary NSCLC. We identify two CD8+ TIL subpopulations expressing memory-like gene modules: one is also present in blood (circulating precursors) and the other one in juxtatumor tissue (tissue-resident precursors). In tumors, these two precursor populations converge through a unique transitional state into terminally differentiated cells, often referred to as dysfunctional or exhausted. Differentiation is associated with TCR expansion, and transition from precursor to late-differentiated states correlates with intratumor T cell cycling. These results provide a coherent working model for TIL origin, ontogeny, and functional organization in primary NSCLC.

scholarly journals Contribution of resident and circulating precursors to tumor-infiltrating CD8+ T cell populations in non-small cell lung cancer patients

2020 ◽  
Author(s):  
Paul Gueguen ◽  
Christina Metoikidou ◽  
Thomas Dupic ◽  
Myriam Lawand ◽  
Christel Goudot ◽  
...  
Keyword(s):  
Lung Cancer ◽  
T Cell ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Functional Organization ◽  
Tumor Infiltrating Lymphocytes ◽  
Cell Receptor ◽  
Small Cell ◽  
Small Cell Lung ◽  
Primary Nsclc

AbstractTumor-infiltrating lymphocytes (TILs) in general, and CD8+ TILs in particular, represent a favorable prognostic factor in non-small cell lung cancer (NSCLC). The tissue origin, regenerative capacities, and differentiation pathways of TIL subpopulations, however, remain poorly understood. Using a combination of single cell RNA and T cell receptor (TCR) sequencing, we investigate the functional organization of TIL populations in primary NSCLC. We identify two CD8+ TIL subpopulations expressing memory-like gene modules: one is also present in blood (circulating precursors) and the other one in juxta-tumor tissue (tissue resident precursors). In tumors, these two precursor populations converge through a unique transitional state into terminally differentiated cells, often referred to as dysfunctional or exhausted. Differentiation is associated with TCR expansion, and transition from precursor to late differentiated states correlates with intratumor T cell cycling. These results provide a coherent working model for TIL origin, filiation and functional organization in primary NSCLC.

T-cell receptor V-gene usage in neoplasms of the central nervous system

1993 ◽  
Vol 78 (4) ◽  
pp. 630-637 ◽  
Author(s):  
Adrian Merlo ◽  
Luis Filgueira ◽  
Markus Zuber ◽  
Antonio Juretic ◽  
Felix Harder ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Tumor Infiltrating Lymphocytes ◽  
Cell Receptor ◽  
Gene Products ◽  
Peripheral Blood Mononuclear ◽  
Infiltrating Lymphocytes

✓ The use of tumor-infiltrating lymphocytes in the treatment of central nervous system (CNS) neoplasms has met with serious obstacles due to difficulty of culture and poor characterization. Since in other tumors the therapeutic effects of tumor-infiltrating lymphocytes have been shown to rely on T-cell receptor engagement, the authors addressed the question as to whether expression of T-cell receptor variable (V) domains in cultured tumor-infiltrating lymphocytes from CNS is different from that of autologous cultured peripheral blood mononuclear cells. Infiltrating lymphocytes from CNS neoplasms, including primary malignancies, metastatic cancers, and meningiomas, were cultured in the presence of interleukin-2 and anti-CD3 monoclonal antibodies (MoAb's) in order to obtain optimum growth of T cells. Autologous peripheral blood mononuclear cells from the same patients were similarly cultured. After 4 to 5 weeks of culture, 97.3% ± 2.6% (mean ± standard deviation) of the resulting cell populations were CD3-positive lymphocytes. The expression of T-cell receptor V domains was then studied by using a panel of 12 MoAb recognizing gene products from T-cell receptor V-α 2, V-β 5, 6, 8, and 12, V-γ 4 and 9 families, and from two subfamilies of V-δ 2. Remarkably, in over 70% of all paired measurements, percentages of T cells expressing discrete T-cell receptor V-gene products were found to be virtually identical in tumor- and peripheral blood-derived cultured cell populations, with differences never exceeding 1%. In contrast, a different expression of individual V-gene products, concerning both α/β and γ/δ T-cell receptors, could be detected between cultured tumor-infiltrating lymphocytes and autologous peripheral blood-derived T lymphocytes in seven of 12 patients. In two cases, significant differences between the two populations were also observed in the proliferative responses obtained upon stimulation with staphylococcal enterotoxins that trigger defined V-β T-cell receptors. Altogether, these data suggest that the T-cell receptor repertoire of cultured tumor-infiltrating lymphocytes from CNS tumors, suitable for use in adoptive immunotherapies, differs from that of autologous cultured peripheral blood mononuclear cells.

Loss of T-cell receptor-CD3ζ and T-cell function in tumor-infiltrating lymphocytes but not in tumor-associated lymphocytes in ovarian carcinoma

Surgery ◽  
2001 ◽  
Vol 129 (6) ◽  
pp. 749-756 ◽  
Author(s):  
Diane C. Lockhart ◽  
Allen K. Chan ◽  
Simona Mak ◽  
Hong-Gu Joo ◽  
Heather A. Daust ◽  
...  
Keyword(s):  
T Cell ◽  
Ovarian Carcinoma ◽  
T Cell Receptor ◽  
Cell Function ◽  
Tumor Infiltrating Lymphocytes ◽  
Cell Receptor ◽  
T Cell Function ◽  
Infiltrating Lymphocytes

scholarly journals Restoring the Association of the T Cell Receptor with CD8 Reverses Anergy in Human Tumor-Infiltrating Lymphocytes

Immunity ◽  
2008 ◽  
Vol 28 (3) ◽  
pp. 414-424 ◽  
Author(s):  
Nathalie Demotte ◽  
Vincent Stroobant ◽  
Pierre J. Courtoy ◽  
Patrick Van Der Smissen ◽  
Didier Colau ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Human Tumor ◽  
Tumor Infiltrating Lymphocytes ◽  
Cell Receptor ◽  
Infiltrating Lymphocytes

A preclinical study of tumor-infiltrating lymphocytes in NSCLC.

2018 ◽  
Vol 36 (5_suppl) ◽  
pp. 161-161
Author(s):  
Lorenzo Federico ◽  
Cara L. Haymaker ◽  
Marie-Andree Forget ◽  
Andrea Ravelli ◽  
Ankit Bhatta ◽  
...  
Keyword(s):  
Lung Cancer ◽  
T Cell ◽  
Small Cell Lung Cancer ◽  
Success Rate ◽  
Ex Vivo ◽  
Tumor Infiltrating Lymphocytes ◽  
Small Cell ◽  
Autologous Tumor ◽  
Small Cell Lung ◽  
Infiltrating Lymphocytes

161 Background: Multiple clinical studies have shown that adoptive cell transfer (ACT) of autologous tumor-infiltrating lymphocytes (TIL) is remarkably effective in melanoma patients. Non-small cell lung cancer (NSCLC) shares similarities with melanoma in terms of mutational burden and sensitivity to immune checkpoint inhibitors. We therefore sought to test whether TIL ACT may represent a viable option for the treatment of NSCLC patients. We utilized tissue collected from patients enrolled on the prospective ImmunogenomiC prOfiling of Non-small cell lung cancer (ICON) study. Methods: TIL and tissue-infiltrating lymphocytes were expanded ex vivo from 97 freshly resected early-stage localized NSCLC tumors and 39 matched uninvolved lung tissues. Growth and functional characteristics of TIL were assessed via flow cytometry, TIL-tumor reactivity assays, and analysis of TCRβ sequencing data. Results: NSCLC showed an increased proportion of CD3+ lymphocytes within the tumor-infiltrating leukocyte component as compared to matched normal lung tissue. The TIL compartment included a suppressed CD8+ T cell subset expressing significantly higher levels of PD-1 and lacking cytolytic potential compared to T cells expanded from normal tissue. TIL contained a higher proportion of proliferating (Ki67+) CD8+CD103+ tissue-resident memory (TRM) cells expressing activation markers such as CTLA4, LAG3, PD1 and ICOS, and increased CD4+ Tregs. Despite a highly immunosuppressive environment, TIL expansion was achieved with a success rate of 68% (n = 97) but appeared hindered in patients undergoing neoadjuvant chemotherapy treatment prior to surgery (56.2%, n = 16 vs 72.5% success rate in therapy-naïve patients). In addition, expansion efficiency (number expanded and time of culture) of TIL and matched lung residing lymphocytes were significantly associated (r = 0.379, p = 0.017, n = 39). Importantly, expanded CD8+ TIL products were oligoclonal and showed reactivity toward autologous tumors. Conclusions: Although NSCLC TIL are functionally inhibited in vivo they can be successfully expanded ex vivo and demonstrate recognition of autologous tumor cells. These data suggest that TIL can potentially be used for adoptive T cell-based immunotherapy in NSCLC.

Analysis of the T Cell Receptor Variability of Tumor-Infiltrating Lymphocytes in Colorectal Carcinomas

Tumor Biology ◽  
1998 ◽  
Vol 19 (3) ◽  
pp. 205-212 ◽  
Author(s):  
P.K. Baier ◽  
S. Wimmenauer ◽  
T. Hirsch ◽  
B.-U. v. Specht ◽  
S. v. Kleist ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Tumor Infiltrating Lymphocytes ◽  
Cell Receptor ◽  
Colorectal Carcinomas ◽  
Infiltrating Lymphocytes
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