Immunological impact of ramucirumab on tumor microenvironment in advanced gastric cancer.

2018 ◽  
Vol 36 (5_suppl) ◽  
pp. 98-98 ◽  
Author(s):  
Yosuke Togashi ◽  
Yasuko Tada ◽  
Daisuke Kotani ◽  
Akihito Kawazoe ◽  
Toshihiko Doi ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
T Cells ◽  
Advanced Gastric Cancer ◽  
Mononuclear Cells ◽  
Low Frequency ◽  
Progression Free Survival ◽  
Tumor Infiltrating Lymphocytes ◽  
Peripheral Blood Mononuclear ◽  
Primary Tumors ◽  
Significant Difference

98 Background: Ramucirumab (RAM), a monoclonal antibody against VEGFR2, was recently approved for the treatment of advanced gastric cancer (GC). However, little is known about the immunological effects in advanced GC patients. Methods: Patients with advanced GC who had been planned to receive chemotherapy containing RAM were prospectively enrolled for this study from January 2016 to September 2016. Paired samples were obtained from peripheral blood mononuclear cells (PBMCs) and tumor infiltrating lymphocytes (TILs) in primary tumors pre- and post-RAM therapy to investigate immune profiles. Results: A total of 59 PBMCs and TILs from 18 patients were collected. Higher frequencies of FOXP3highCD45RA-CD4+ T cells (effector regulatory T cells: eTregs) were detected in TILs compared with PBMCs (19.05±10.48% vs 1.89±1.0%, P < 0.0001), and the presence of high eTreg in TILs was not reflected in PBMCs. eTregs of TILs, but not of PBMC were significantly decreased after RAM-containing therapies (22.67±11.19% vs. 16.33±8.44%, P = 0.034). Expressions of immune checkpoint (IC) molecules (PD-1, CTLA-4, LAG-3, and ICOS) were much higher in TILs than those in PBMCs, and all these molecules exhibited higher expressions on eTregs than on CD8+ T cells. Among them, ICOS was specifically expressed by eTregs in TILs. PD-1+CD8+ T cells in TILs were significantly decreased after RAM-containing therapies (54.99±19.06% vs. 39.23±17.15%, P = 0.0005), but not in PBMC. Patients with partial responses had significantly higher frequency of eTreg in pre-treatment TIL than those with progression disease (32.56±12.11% vs. 14.83±3.18%, P = 0.036). Furthermore, patients with high eTreg frequency had significantly longer progression-free survival than those with low frequency (161 days vs. 76 days, P = 0.024). Conclusions: There was significant difference in immune profile between PBMC and TIL in GC patients. eTregs and PD-1 expression on CD8+T cells in TILs, not in PBMCs were decreased after RAM-containing therapies. This observation suggests the importance of TIL analyses and might be a rationale to use RAM as an immunomodulator in combination with IC inhibitors.

scholarly journals Helios Expression in Tumor-Infiltrating Lymphocytes Correlates with Overall Survival of Advanced Gastric Cancer Patients

Life ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 189
Author(s):  
Wei-Ming Chen ◽  
Jing-Lan Liu ◽  
Huei-Chieh Chuang ◽  
Yong-Lin Chang ◽  
Chia-Ming Yeh ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
T Cells ◽  
Cancer Patients ◽  
Peripheral Blood Mononuclear Cells ◽  
Mononuclear Cells ◽  
Tumor Infiltrating Lymphocytes ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells ◽  
Gastric Cancer Patients ◽  
Infiltrating Lymphocytes

Immunotherapy is a highly promising approach for the treatment of gastric cancer, the third-leading cause of overall cancer death worldwide. In particular, tumor-infiltrating lymphocytes and peripheral blood mononuclear cells are believed to mediate host immune responses, although this activity may vary depending on the activation status and/ or their microenvironments. Here, we examined the expression of a specific zinc finger transcription factor, Helios (IKZF2), in gastric tumor-infiltrating lymphocytes by immunohistochemistry and the correlation with survival. Segregation of gastric cancer patients into high- vs. low-Helios-expressing tumor-infiltrating lymphocytes showed those with high expression to exhibit longer survival in gastric cancer patients, Helicobacter pylori-infected gastric cancer patients and advanced stage (III–IV) gastric cancer patients. In particular, Helios expression was an independent factor for survival in advanced gastric cancer patients. We performed immunofluorescence staining to detect Helios expression in tumor-infiltrating lymphocytes and peripheral blood mononuclear cells. We found that Helios is expressed more in CD4+ T cells and little in CD8+ T cells in infiltrated lymphocytes in gastric cancer. In summary, we believe that the study of specific characteristics of tumor-infiltrating lymphocytes can delineate the interactions of immune and tumor cells to improve upon immunotherapy strategies.

scholarly journals Impaired Lymphocyte Profile in Schistosomiasis Patients with Periportal Fibrosis

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Luciana Santos Cardoso ◽  
Andréia de Souza Rocha Barreto ◽  
Jamille Souza Fernandes ◽  
Ricardo Riccio Oliveira ◽  
Robson da Paixão de Souza ◽  
...  
Keyword(s):  
T Cells ◽  
Mononuclear Cells ◽  
Low Frequency ◽  
Activated T Cells ◽  
Peripheral Blood Mononuclear ◽  
Cross Sectional ◽  
Periportal Fibrosis ◽  
Th2 Immune Response ◽  
Significant Difference ◽  
Severe Fibrosis

The Th2 immune response in chronic schistosomiasis is associated with the development of periportal fibrosis. However, little is known about the phenotype and activation status of T cells in the process.Objective. To evaluate the profile of T cells in schistosomiasis patients with periportal fibrosis.Methods. It was a cross-sectional study, conducted in the village of Agua Preta, Bahia, Brazil, which included 37 subjects with periportal fibrosis determined by ultrasound. Peripheral blood mononuclear cells were obtained by the Ficcol-hypaque gradient and the frequency of T cells expressing the surface markers CD28, CD69, CD25, and CTLA-4 was determined by flow cytometry.Results. The frequency of CD4+CD28+T lymphocytes was higher in individuals with moderate to severe fibrosis compared to patients with incipient fibrosis. We did not observe any significant difference in the frequency of CD4+T cells expressing CD69 among groups of individuals. There was also no significant difference in the frequency of CD8+T cells expressing CD28 or CD69 among the studied groups. Individuals with moderate to severe fibrosis presented a lower frequency of CD8+T cells, CD4+CD25highT cells, and CD4+CTLA-4+T cells when compared to patients without fibrosis or incipient fibrosis. The frequency of CD4+CD25lowcells did not differ between groups.Conclusion. The high frequency of activated T cells coinciding with a low frequency of putative Treg cells may account for the development of periportal fibrosis in human schistosomiasis.

scholarly journals Alterations in regulatory T cells and immune checkpoint molecules in pancreatic cancer patients receiving FOLFIRINOX or gemcitabine plus nab-paclitaxel

2021 ◽  
Author(s):  
L. Sams ◽  
S. Kruger ◽  
V. Heinemann ◽  
D. Bararia ◽  
S. Haebe ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Regulatory T Cells ◽  
Cd8 T Cells ◽  
Mononuclear Cells ◽  
Progression Free Survival ◽  
Ductal Adenocarcinoma ◽  
Immune Checkpoints ◽  
Prognostic Information ◽  
Peripheral Blood Mononuclear

Abstract Purpose This pilot study aimed on generating insight on alterations in circulating immune cells during the use of FOLFIRINOX and gemcitabine/nab-paclitaxel in pancreatic ductal adenocarcinoma (PDAC). Patients and methods Peripheral blood mononuclear cells were isolated before and 30 days after initiation of chemotherapy from 20 patients with advanced PDAC. Regulatory T cells (FoxP3+) and immune checkpoints (PD-1 and TIM-3) were analyzed by flow cytometry and immunological changes were correlated with clinical outcome. Results Heterogeneous changes during chemotherapy were observed in circulating T-cell subpopulations with a pronounced effect on PD-1+ CD4+/CD8+ T cells. An increase in FoxP3+ or PD-1+ T cells had no significant effect on survival. An increase in TIM3+/CD8+ (but not TIM3+/CD4+) T cells was associated with a significant inferior outcome: median progression-free survival in the subgroup with an increase of TIM-3+/CD8+ T cells was 6.0 compared to 14.0 months in patients with a decrease/no change (p = 0.026); corresponding median overall survival was 13.0 and 20.0 months (p = 0.011), respectively. Conclusions Chemotherapy with FOLFIRNOX or gemcitabine/nab-paclitaxel induces variable changes in circulating T-cell populations that may provide prognostic information in PDAC.

Reproducibility and Robustness of the Xcellerate III Process for the GMP Manufacture of Xcellerated T Cells™ for Infusion into CLL Patients.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4995-4995
Author(s):  
Lisa Hami ◽  
Cherie Green ◽  
Katharine Miller ◽  
Stewart Craig
Keyword(s):  
T Cells ◽  
Cell Viability ◽  
T Cell Activation ◽  
Cell Activation ◽  
Mononuclear Cells ◽  
Total Cell ◽  
Cell Yield ◽  
P Value ◽  
Peripheral Blood Mononuclear ◽  
Significant Difference

Abstract Autologous peripheral blood mononuclear cells (PBMC) cryopreserved from a leukapheresis collection comprise the starting cellular source for the Wave® Bioreactor-based Xcellerate III Process [Hami et al, Bioprocessing Journal2003: 2; 23–32] used for the GMP manufacture of Xcellerated T Cells. For an ongoing clinical trial, n=13 patients have been infused with products manufactured from PBMC cryopreserved and stored in the vapor phase of liquid nitrogen (LN2) for 2–9 days before use in the Xcellerate III Process. This clinical protocol was recently amended to allow patients to receive a 2nd infusion of Xcellerated T Cells. To date, 2nd products have been manufactured for 11 of the CLL patients using the original PBMC that had been stored cryopreserved for up to 7 months from collection. Comparison of the processes for the manufacture of 1st (n=13) and 2nd (n=11) infusion products shows: • No significant difference in the in-process T cell activation as determined by increase in cell size, up-regulation of CD25 & up-regulation of CD154 expression (refer to Figure 1). Figure Figure • The total cell yield for 2nd infusion products is within one (1) standard deviation of the average for the manufacture of the 1st infusion product (refer to Table 1). • No significant difference in cell viability, CD3+ purity, or CD4:CD8 ratio for the final Xcellerated T Cells product (refer to Table 1). Table 1. Final Product Characteristics Final Product (Day 13) Average±S.D. p value 1st Infusion (n=13) 2nd Infusion (n=11) Total Cell Yield (x109) 0.01 137 ± 35 104 ± 17 Cell Viability (%) 0.15 93.5 ± 3.4 91.6 ± 2.4 CD3+ Purity (%) <0.001 98.4 ± 1.1 99.0 ± 0 CD4:CD8 Ratio 0.32 8.5 ± 7.7 5.7 ± 4.5 These data demonstrate high reproducibility and robustness of the Xcellerate III Process when using PBMC from the same leukapheresis collection in sequential processing runs. In addition, these data demonstrate that cryopreserved PBMC can be stored for many months prior to their use as the starting material in the Xcellerate III Process. Xcyte™, Xcyte Therapies™, Xcellerate™, Xcellerated T Cells™ and the circle logo are trademarks of Xcyte Therapies, Inc.

Salvage gastrectomy for unresectable advanced gastric cancer after combination chemotherapy with docetaxel, cisplatin, and S-1.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e15113-e15113
Author(s):  
Kei Hosoda ◽  
Keishi Yamashita ◽  
Shinichi Sakuramoto ◽  
Hiroaki Mieno ◽  
Katsuhiko Higuchi ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Lymph Node ◽  
Advanced Gastric Cancer ◽  
Univariate Analysis ◽  
Pancreatic Head ◽  
Progression Free Survival ◽  
Hematologic Toxicity ◽  
Primary Tumors ◽  
Free Survival

e15113 Background: The prognosis for patients with unresectable advanced gastric cancer treated with chemotherapy alone is extremely poor. We have evaluated the safety and efficacy of salvage gastrectomy following chemotherapy with docetaxel, cisplatin, and S-1 (DCS) in patients with unresectable advanced gastric cancer. Methods: We evaluated 30 patients with unresectable advanced gastric adenocarcinoma whose lesions were down-staged by DCS chemotherapy and who underwent salvage gastrectomy with lymph node dissection from 2006 to 2012, when visible lesions were judged resectable. We retrospectively reviewed their medical records to identify factors that would influence overall survival. Results: Of the 30 patients, 17 had extra-regional lymph node metastases, 5 had liver metastases, 9 had peritoneal dissemination and 6 had pancreatic head invasion prior to DCS chemotherapy. Of the 30 patients, 23, 3, and 4 underwent R0, R1, and R2 resection, respectively. No in-hospital deaths or reoperations occurred. Pathological evaluation of primary tumors revealed grades 3, 2, 1b, 1a, and 0 tumor regression in 4, 9, 7, 7, and 2 patients, respectively. Median progression-free survival was 19 months.Two-year progression-free survival and overall survival rates were 45% and 65%, respectively. Of 17 patients with target tumors, 15 had partial responses, making the overall response rate 88%. The most common grade 3/4 hematologic toxicity was neutropenia (56%); all treatment-related toxicities were resolved, and no patient died of toxicity-related causes. Univariate analysis showed that R1/2 surgery (p<0.001), diffuse type histology (p=0.054), histological grade 0/1a/1b following chemotherapy (p<0.033), ypN3 (p<0.001) and yply2/3 (p=0.003), were significantly prognostic of reduced overall survival. A multivariate proportional hazard model found that ypN3 (p=0.003) was the sole independent prognostic factor. Conclusions: Salvage gastrectomy after DCS chemotherapy was safe and effective in patients with unresectable advanced gastric cancer. Lymph node metastasis after chemotherapy was significantly prognostic of poor prognosis, suggesting the need for further treatment.

Effect of vorinostat (VOR) and hydroxychloroquine (HCQ) on immunity and autophagy in metastatic colorectal cancer (mCRC).

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 670-670
Author(s):  
Sukeshi R. Patel ◽  
Vincent Hurez ◽  
Steffan T Nawrocki ◽  
Martin Goros ◽  
Joel Michalek ◽  
...  
Keyword(s):  
T Cells ◽  
Tumor Immunity ◽  
Mononuclear Cells ◽  
Phase 1 ◽  
Progression Free Survival ◽  
Peripheral Blood Mononuclear ◽  
Lysosomal Protease ◽  
Grade 5 ◽  
Grade 3 ◽  
Expansion Cohort

670 Background:HCQ enhances the anti-cancer activity of the histone deacetylase inhibitor, VOR in pre-clinical CRC models. Our phase 1 dose escalation trial found that patients (pts) with mCRC obtained prolonged clinical benefit from VOR + HCQ. Thus, a single arm expansion cohort in refractory mCRC was done. Methods: Pts with refractory mCRC received VOR 600 mg by mouth (PO) + HCQ 400 mg PO daily, in a 3-week cycle. The primary endpoint was median progression-free survival (mPFS). Secondary endpoints: median overall survival (mOS), adverse events (AE) (NCI-CTCAEv3.0), flow cytometry (FACS) of peripheral blood mononuclear cells (PBMCs), tumor biopsies. Results: 20 pts were enrolled (19 evaluable for survival): mean age 61 (44-74). Female 7/male 23, 9 Caucasian/10 Hispanic/1 Black, 11 KRAS mutated. ECOG 0-1 (18 pts). 3+ prior lines (13), previous regorafenib (4). Dose level reduction on study (7). mPFS 2.8 months (95% CI: 1.63-8.16). mOS 6.7 months (95% CI: 4.63-NR). Treatment-related grade 3 AEs: nausea/vomiting (3), anemia (3). Grade 4 thrombocytopenia (3). Grade 4 INR elevation (1 pt on Coumadin). No grade 5 AEs. Five pts (26%) had stable disease ≥12 weeks. Treatment significantly reduced regulatory and PD-1+ (exhausted) CD4+ and CD8+ T cells and increased CD45RO+CD62L-CD4+ (effector) T cells, consistent with improved anti-tumor immunity. On-study biopsies (3) showed increased lysosomal protease CTSD and LC3-II consistent with autophagy inhibition. Conclusions: VOR/HCQ is active, safe and tolerated in refractory CRC patients, resulting in potentially improved anti-tumor immunity (decreased exhausted and regulatory T cells and increased effector phenotype T cells) and reduced tumor autophagy. A randomized phase II trial of VOR/HCQ versus regorafenib is now open. Clinical trial information: NCT01023737.

scholarly journals Expression of inhibitory receptors on CD4+ and CD8+ T cells from healthy Colombian donors

2012 ◽  
Vol 17 (1) ◽  
pp. 35
Author(s):  
Alejandra Rico- Lombana Rico- Lombana ◽  
Jose Mateus ◽  
Paola Lasso ◽  
John Mario González ◽  
Concepción Judith Puerta ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell Activation ◽  
Cd8 T Cells ◽  
Cell Activation ◽  
Mononuclear Cells ◽  
Inhibitory Receptors ◽  
Peripheral Blood Mononuclear ◽  
Programmed Death ◽  
Significant Difference ◽  
Programmed Death 1

<p>T cell activation involves positive cellular signals that promote effector functions and negative signals that contribute to the regulation of these responses. These regulatory signals are generated upon activation of receptors on T cells that include CD160, 2B4, Programmed Death-1 and CTLA-4. <strong>Objective</strong>. To evaluate the expression of inhibitory receptors like CD160, 2B4, Programmed Death-1 and CTLA-4 on CD4+ and CD8+ T cells from healthy Colombian donors. <strong>Materials and methods</strong>. Peripheral blood mononuclear cells from 30 healthy donors from Bogotá (Colombia) were obtained via Ficoll-Hypaque density gradient and cells were stained with specific conjugated antibodies previously titrated. <strong>Results</strong>. The CD160, 2B4, and Programmed Death-1 inhibitory markers were detected on CD4+ T cells<br />with expression levels of 0.35%, 1.04%, and 1.35%, respectively. On CD8+ T cells, these markers were expressed at higher levels: 16%, 8.97%, and 4.3%, respectively. In contrast to the other receptors, CTLA-4 frequency of expression showed no significant difference between CD4+ (1.56%) and CD8+ (1.53%) T cells. Frequency of CD160/2B4 and CTLA-4/ Programmed Death-1 coexpression was 0.18% and 0.09% on CD4+ cells, and 4.02% and 0.2% on CD8+ T cells. <strong>Conclusions</strong>. This is the first report showing the frequency of inhibitory receptors such as CD160, 2B4, Programmed Death-1, and CTLA-4 on CD4+ and CD8+ T cells from healthy Colombian donors. Our findings serve as a baseline for the analysis and comparison of these receptors in Colombian populations with different disease conditions.</p><p><br /><strong>Key words</strong>: inhibitory receptors, T cells</p>

CD4+ T cells in PBMC to predict the outcome of anti-PD-1 therapy.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 11525-11525 ◽  
Author(s):  
Hiroshi Kagamu ◽  
Ou Yamaguchi ◽  
Ayako Shiono ◽  
Atsuto Mouri ◽  
Sachiko Miyauchi ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Chemokine Receptors ◽  
Mononuclear Cells ◽  
Surrogate Marker ◽  
Progression Free Survival ◽  
Cell Subpopulation ◽  
Peripheral Blood Mononuclear ◽  
Significant Prolongation ◽  
Nsclc Patients

11525 Background: Antibody blockade of programmed death 1 (PD-1), has led to durable responses and significant prolongation of overall survival in metastatic cancers including non-small cell lung cancer (NSCLC). However, in clinical trials, response rates were as low as 20 %, and approximately 50 % of the patients did not achieve benefits to prolong progression free survival. These results bring us a hypothesis that there are subgroups with distinct pre-existing anti-tumor immunity resulting in different responses to anti-PD-1 therapy. We reported that effector T cells, which are capable of mediating antitumor reactivity, are primed in LNs draining growing tumors and that these T cells exclusively belong to the T cells that down-regulated CD62L (CD62Llow) subpopulation. In the absence of purified tumor antigenic proteins or peptides on many tumors, the expression of the homing molecule CD62L on T cells may serve as a surrogate marker for identifying tumor-specific immune cells. Methods: We analyzed the peripheral blood mononuclear cells (PBMC) of 50 consecutive NSCLC patients who were planned to be treated with anti-PD-1 Ab, Nivolumab after obtaining written informed consent. The patients received Nivolumab at a dose of 3 mg per kilogram of body weight every 2 weeks. Tumor response was assessed with the use of the Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1, at week 8 and every 8 weeks thereafter. Results: The NSCLC patients who achieved partial response (PR) or stable disease (SD) had significantly (p = 4.1x10-7) more CD62Llow CD4+ T cells in PBMC than progressive disease (PD) patients. The percentages of CD62Llow in CD4+ T cells provided sensitivity 92.9 %, and specificity 96.7 % to predict the patients who had PD. Moreover, SD patients had significantly (p = 0.0067) less regulatory T cell subpopulation than PR patients, thus, it was possible to predict PR from SD. Conclusions: These results show that the major differences in pre-existing immunity among PR, SD, and PD patients to anti-PD-1 Ab existed in CD4+ T cell balance between primed effector and regulatory T cells. Further characterization of CD62Llow CD4+ T cells including mRNA microarray, checkpoint molecules, and chemokine receptors is going on.

scholarly journals PD-L1 Expression and CD8+ T Cell Infiltration Predict a Favorable Prognosis in Advanced Gastric Cancer

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Yangyang Wang ◽  
Chunchao Zhu ◽  
Wei Song ◽  
Jun Li ◽  
Gang Zhao ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
T Cells ◽  
T Cell ◽  
Advanced Gastric Cancer ◽  
High Density ◽  
Cell Infiltration ◽  
Cox Regression Analysis ◽  
T Cell Infiltration ◽  
Programmed Death ◽  
Significant Difference

Advanced gastric cancer (AGC) has high morbidity and mortality in East Asia, and it is urgent to explore new treatments to improve patient prognosis. Programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors have exhibited remarkable activity in clinical trials and were approved by the FDA for clinical therapy in several types of tumors. Here, we evaluated PD-L1 expression and T cell infiltration in AGC. Positive tumor PD-L1 expression was detected in 171 AGCs (33.60%) out of 509 AGCs. PD-L1 expression was positively correlated with CD8+ T cell infiltration. Then, PD-L1 and CD8A mRNA expression was analyzed using gastric cancer data from the TCGA database, confirming a positive correlation. Patient survival was assessed according to PD-L1 status and the T cell infiltration density. PD-L1 expression and a high density of CD8+ T cells in AGCs were associated with improved prognosis, whereas no significant difference was noted between PD-1 and CD3 expression. In contrast, a high density of FOXP3+ T cells in AGCs indicated a poor prognosis. Multivariate Cox regression analysis revealed that CD8+ T cell density acts as an independent predictor of overall survival (OS) in AGC patients. Taken together, this study further highlights targets for immune checkpoint-based therapy in AGC.

scholarly journals Cross-reactive memory T cells associate with protection against SARS-CoV-2 infection in COVID-19 contacts

2022 ◽  
Vol 13 (1) ◽  
Author(s):  
Rhia Kundu ◽  
Janakan Sam Narean ◽  
Lulu Wang ◽  
Joseph Fenn ◽  
Timesh Pillay ◽  
...  
Keyword(s):  
T Cells ◽  
Immune Responses ◽  
Mononuclear Cells ◽  
Memory T Cells ◽  
Peripheral Blood Mononuclear ◽  
Protective Function ◽  
Host Protection ◽  
Household Contacts ◽  
Significant Difference ◽  
Membrane Envelope

AbstractCross-reactive immune responses to SARS-CoV-2 have been observed in pre-pandemic cohorts and proposed to contribute to host protection. Here we assess 52 COVID-19 household contacts to capture immune responses at the earliest timepoints after SARS-CoV-2 exposure. Using a dual cytokine FLISpot assay on peripheral blood mononuclear cells, we enumerate the frequency of T cells specific for spike, nucleocapsid, membrane, envelope and ORF1 SARS-CoV-2 epitopes that cross-react with human endemic coronaviruses. We observe higher frequencies of cross-reactive (p = 0.0139), and nucleocapsid-specific (p = 0.0355) IL-2-secreting memory T cells in contacts who remained PCR-negative despite exposure (n = 26), when compared with those who convert to PCR-positive (n = 26); no significant difference in the frequency of responses to spike is observed, hinting at a limited protective function of spike-cross-reactive T cells. Our results are thus consistent with pre-existing non-spike cross-reactive memory T cells protecting SARS-CoV-2-naïve contacts from infection, thereby supporting the inclusion of non-spike antigens in second-generation vaccines.

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