Psychosocial factors, such as social support and distress, are associated with changes in the cellular immune response, not only in peripheral blood, but also at the tumor level. These relationships were more robust in TIL. These findings support the presence of stress influences in the tumor microenvironment.

The adaptive immune response of ovarian cancer patients has been linked to survival, and is known to be impaired in the tumor microenvironment. Little is known about relationships between biobehavioral factors such as depressed mood and anxiety and the adaptive immune response in ovarian cancer. Thirty-seven patients with epithelial ovarian cancer and 14 patients with benign neoplasms completed psychosocial questionnaires pre-surgery. Lymphocytes from peripheral blood, tumor, and ascites (fluid around the tumor), were obtained on the day of surgery. Expression of the Type-1 cytokine interferon gamma (IFNγ), and the Type-2 cytokine interleukin-4 (IL-4) by T-helper (CD4 + ) and T-cytotoxic (CD8 + ) cells was measured under autologous tumor-stimulated, polyclonally-stimulated, or unstimulated conditions. Links with mood were examined. Among cancer patients, marked elevations in unstimulated and tumor-stimulated Type-2 responses were seen, particularly in ascites and tumor-infiltrating lymphocytes (P values < 0.01). With polyclonal stimulation, lymphocytes from all compartments expressed elevated Type-1 cytokines (P values <0.014). Depressed and anxious mood were both associated with significantly lower ratios of polyclonally-stimulated CD4 + cells producing IFNγ (TH 1 cells) vs. IL-4 (TH 2 cells) in all compartments (depressed mood: P = 0.012; anxiety: P = 0.038) and depressed mood was also related to lower ratios of polyclonally-stimulated CD8 + cells producing IFNγ (TC 1 ) vs. IL-4 (TC 2 ) (P =0.035). Although effects of polyclonal stimulation should be generalized with caution to the in vivo immune response, findings suggest that depressed and anxious mood are associated with greater

Psychosocial factors are known to be associated with properties of both NK cells and T cells in cancer patients. Less is known about the relationship between psychosocial factors and NKT cells, a rare group of lymphocytes that have known relevance for tumor control. We examined four psychosocial factors and percentage and number of CD3 + CD56 + NKT cells, CD3 − CD56 + NK cells, and CD3 + CD56 − T cells in peripheral blood lymphocytes (PBL), ascites, and tumor of 35 ovarian cancer patients and 28 patients with benign pelvic masses. Patients awaiting surgery for a suspected cancerous mass completed questionnaires and gave a pre-surgical blood sample. Ascites and tumor were taken during surgery. After lymphocyte isolation, subpopulations were analyzed by flow cytometry. Benign and cancer patients did not differ on PBL subpopulations. Among cancer patients, NKT cell percentage was significantly higher in tumor and ascites than in PBL; T cell percentage was significantly higher in PBL than tumor. NKT, NK, and T cell number were significantly higher in peripheral blood than in ascites. Positive reframing was related to significantly higher NKT cell percentage and number in PBL. Social support was related to significantly higher NKT cell percentage in tumor. Vigor was related to significantly higher NKT cell percentage in PBL. Total mood disturbance was not related to NKT cell percentage or number. No significant relationships were found between psychosocial factors and NK cell percentage and number and T cell percentage and number. Given the anti-tumor activity of CD3 + CD56 + cells, these relationships may have relevance for cancer control.

Objective To evaluate patterns of recurrence for ovarian, fallopian tube, and primary peritoneal cancer patients undergoing extended treatment with bevacizumab (BEV). Methods A retrospective review of patients with primary ovarian, fallopian tube, or peritoneal cancer treated with BEV alone or in combination with other chemotherapy from 2001 to 2011 was performed. Qualified patients were identified by chemotherapy records. Electronic medical records, labs, and imaging reports were reviewed and abstracted. Results Of 108 patients identified, 89 patients met study criteria by having disease progression either during treatment with BEV or after discontinuing BEV without initiating any other treatment. Patients on extended BEV therapy (> 12 cycles) were more likely to recur in extra-visceral sites (p = 0.04), especially in lymph nodes (p = 0.0002), and presented with fewer symptoms at time of recurrence (p = 0.02), compared to patients who had received ≤ 12 cycles. CA-125 becomes less reliable for the detection of recurrent disease with extended BEV therapy (p = 0.03 for ≤ 12 cycles vs. p = 0.08 for >12 cycles). Radiology was superior to CA-125, symptom, and physical exam, in detecting recurrence with extended BEV therapy (all p < 0.0001). Conclusions Extended treatment with BEV in ovarian, fallopian tube, and peritoneal cancers results in alterations in the patterns of recurrence. Radiologic imaging is more reliable than CA-125, symptoms, or physical exam, in identifying recurrent disease in patients undergoing BEV treatment. As novel targeted therapies continue to be employed, guidelines for gynecologic cancer surveillance must continue to be reexamined.