Characteristics of immune memory and effector activity to cancer-expressed MHC class I phosphopeptides differ in healthy donors and ovarian cancer patients

2021 ◽  
pp. canimm.0111.2021
Author(s):  
Amanda M Lulu ◽  
Kara L Cummings ◽  
Erin D Jeffery ◽  
Paisley T Myers ◽  
Dennis Underwood ◽  
...  
2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 3603-3603
Author(s):  
Lisa Villabona ◽  
Giuseppe V. Masucci ◽  
Peter Ragnhammar

3603 Background: HLA-A*02, a common allele in the Scandinavian population, is a negative prognostic factor in epithelial ovarian cancer. It is a strong predictor of patient outcome, only inferior to clinical staging. This prognostic trait in epithelial ovarian cancer is stronger by the presence of the gene compared with the expression of its protein, MHC class I. Microsatellite instability (MSI) is used as a biomarker for prognosis and is suggested an increased tumor mutational burden which can make the tumor more susceptible for T cell mediated immunotherapy. Our aim was to analyze the prognostic markers HLA-A*02 genotype, MHC class I on tumor cells, the CD8+ lymphocyte infiltration and MSI status in colon cancer patients with randomized treatment. Methods: Clinical information and primary tumors were collected from 520 colon cancer patients and followed for overall survival for 120 months. Patients hade stage II and III colon cancer and were randomized to surgery alone or surgery and adjuvant chemotherapy. HLA-A*02 genotype was determined by conventional PCR. MHC class I, MSI status and CD8+ lymphocyte infiltration were determined by immunohistochemistry. Results: Female patients with a stage III tumor and HLA-A*02 genotype had a better outcome if they had received adjuvant chemotherapy instead of just surgery (p = 0.03), whereas this was not the case for patients with other HLA-A genotypes or in the male patients where HLA-type did not correlate to outcome. MHC class I expression did not act as a prognostic factor, however the presence of CD8+ lymphocytes in the invasive margin and inside the tumor was a positive prognostic factor for overall survival (p = 0.01), although only statistically significant in the male patients (p = 0.03). 21% patients had a tumor with MSI (23% of the female and 19% of the male patients respectively). MSI tumors had a slightly better outcome and this was irrespective of gender and HLA-type. Conclusions: The prognostic traits of HLA-A*02 appear in this colon cancer cohort to act differently in male and female patients. Also CD8+ infiltration is different between genders. These findings suggest that men and women may have two different immune responses to malignancy.


2008 ◽  
Vol 110 (3) ◽  
pp. 365-373 ◽  
Author(s):  
Ninke Leffers ◽  
Annechien J.A. Lambeck ◽  
Pauline de Graeff ◽  
Astrid Y. Bijlsma ◽  
Toos Daemen ◽  
...  

2006 ◽  
Vol 24 (26) ◽  
pp. 4254-4261 ◽  
Author(s):  
Keith L. Knutson ◽  
Christopher J. Krco ◽  
Courtney L. Erskine ◽  
Karin Goodman ◽  
Linda E. Kelemen ◽  
...  

Purpose Studies have demonstrated that the generation of immunity to tumor antigens is associated with improved prognosis for many cancers. A candidate antigen is the folate receptor alpha (FRα), which is overexpressed in breast and ovarian cancers. Our goal in this study was to attain a better understanding of the extent of endogenous FRα immunity. Methods Using a CD4+ T cell epitope prediction algorithm, we predicted promiscuous epitopes of FRα, and tested for immunity in 30 breast (n = 17) or ovarian (n = 13) cancer patients and 18 healthy donors using enzyme-linked immunospot analysis. Results Fourteen peptides were predicted, seven each from the carboxy- and amino-terminus halves of the protein. More than 70% of patients demonstrated immunity to at least one FRα peptide. Patients responded to an average of 3 ± 0.5 peptides, whereas healthy donors responded to 1 ± 0.4 peptides (P = .004). Five peptides were recognized by more than 25% of patients. Responses to three peptides were higher (P < .05) in patients than in healthy donors, suggesting augmented immunity. Compared with healthy individuals, patients developed higher immunity to the amino-terminus half of the receptor (P = .03). There was no difference between each group in the responses to nonspecific (P = .2) and viral stimuli (P = .5). Lastly, patients demonstrated elevated levels of FRα antibodies consistent with a coordinated immune response. Conclusion These findings demonstrate that the FRα is a target of the immune system in breast and ovarian cancer patients. Understanding which antigens are targeted by the immune system may be important for prognosis or immune-based therapies.


2011 ◽  
Vol 17 (10) ◽  
pp. 3408-3419 ◽  
Author(s):  
Michael A. Morse ◽  
Angeles A. Secord ◽  
Kimberly Blackwell ◽  
Amy C. Hobeika ◽  
Gomathinayagam Sinnathamby ◽  
...  

2008 ◽  
Vol 21 (4) ◽  
pp. 435-442 ◽  
Author(s):  
Yuefei Yu ◽  
Petra Pilgrim ◽  
Wei Zhou ◽  
Nicoletta Gagliano ◽  
E. Eldo Frezza ◽  
...  

2012 ◽  
Vol 75 (11) ◽  
pp. 3270-3290 ◽  
Author(s):  
Vivekananda Shetty ◽  
Zacharie Nickens ◽  
James Testa ◽  
Julie Hafner ◽  
Gomathinayagam Sinnathamby ◽  
...  

2015 ◽  
Vol 10 (3) ◽  
pp. 524
Author(s):  
Jing Yao Wang ◽  
Nan Zhang ◽  
Xiaojie Yang ◽  
Danli Gao ◽  
Lirong Yin ◽  
...  

<p>The purpose of this study is to assess whether MHC class I-presented tumor antigen is appraisable for T-cell responses against ovarian cancer. In ovarian cancer cell, human leukocyte antigen A2 (HLA-A2) associated with peptides was used to promote the activation of naive T cells so as to activate antigen-specific T cells. 7 or 4 patients were observed grade 1 or 2 injection site reactions, respectively. 5, 2 or 1 patients were observed grade 1, 2 or 3 pain reactions, respectively. 4 or 1 patients were observed grade 1 or 2 induration reactions. Total number mean value of patients experiencing response to the particular peptide was 7.73, and total number mean value of peptides to which the patients responded was 7.45. MHC class I-presented tumor antigen is appraisable for T-cell responses against ovarian cancer in China.</p>


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