CA72‑4 was first described by Colcher et al in 1981[10]. It is a glycoprotein with a molecular mass > 1000 kDa and is a tumor marker for numerous cancers, including breast, ovarian, colorectal and pancreatic cancer, and it has good specificity for GC [11, 12]. In the literature, CA72-4 was associated with advanced tumor stage, lymph node metastasis, and distant metastasis [13–19]. However, there are few studies on predictive screening or early detection particularly for CA72-4. The analysis showed that CA72-4 was the preferable single test, with a sensitivity value (93.83%) that was higher than that of CEA (72.20%) and much higher than that of CA19-9 (22.30%) [20]. In this study, CA72-4 appeared to be also the most sensitive and specific marker in the gastric cancer patient. At the beginning of treatment, the level of CA72-4 decreased from 35.26 U/mL to 18.24 U/mL, which can be seen as a response to treatment. However, the level of CA72-4 increased from 12.37 U/mL to 86.34 U/mL during the three follow-up after chemotherapy. Because of the rapid increase of CA72-4 levels, we are worried about the risk of recurrence and metastasis despite the abdominal CT scan showed no abnormality.
On November 2016, the patient began to receive NK cells immunotherapy. In our study, we improved the preparation method of NK cells. Our technique resulted in a high yield of at least 1.0 × 1010 NK cells. These NK cells showed evident cytotoxicity against gastric cancer cell lines in vitro. One week after the NK cells infusion, the level of CA72-4 dropped to 16.68 U/mL (Table 1). For the next three years, the patient continued to receive NK cells immunotherapy. In the lately fellow-up, the level of CA72-4 had dropped to the normal and the abdominal CT scan also found no abnormality.
Currently, surgical resection is still the primary treatment for many solid malignancies, however, scattered tumor cells that remain after resection of the primary tumor, may be the main trigger factor for disease recurrence [21]. Furthermore, surgical procedures may induce the release of immunosuppressing factors that render host immune surveillance ineffective, ultimately leading to the increased metastatic disease or recurrence following surgery [22]. Natural killer (NK) cells are cytotoxic lymphocytes that constitute a major component of the innate immune system. NK cell dysfunction following surgery has been documented in both human patients [23–25] and animal models [26, 27]. Rate of local recurrence following surgical tumor resection of colorectal cancer correlated with lower NK cell levels [28]. Correlations between reduced NK cytotoxicity and incidence of metastasis have been established in head and neck as well as pharyngeal cancer [29–31]. These examples highlight the potential for NK cell immunotherapies to improve patient outcomes [32].
Traditional postoperative adjuvant radio/chemotherapy may eliminate residual lesions and reduce tumor recurrence to some extent, but, pure adjuvant radio/chemotherapy primarily kills actively proliferating tumor cells rather than relatively indolent cancer stem cells, which are mainly responsible for recurrence [33, 34]. In addition, SRCC is thought to be less chemosensitive than non-SRCC. Therefore, a novel postoperative adjuvant treatment is urgently needed to improve clinical outcomes for these patients.
Pay an attention to the immune state of patients through detection of the level of lymphocyte subsets including percentage and number timely and accurately, it will help us to evaluate conditions of prognosis and adjust the treatment program for patients. Here we designed to investigate the percentages of CD3 + T, CD3 + CD4 + T, CD3 + CD8 + T, B and NK cells in peripheral blood of the patient using a single-platform flow cytometry-based method, and to analyze the immune function of the patient when the tumor marker CA72-4 increased to the level of 86.34 U/mL. As a result, a lower percentage of CD3 + T and NK cells were observed (Fig. 2), it states that the patient' immune function is impaired. However, there is untapped potential in the use of immunotherapies to reverse or prevent surgical stress-induced NK cell dysfunction. As for the critical role in the anti-tumor immune response of NK cells, we adopt the way of infusion the expansion of NK cells in vitro to repair the damaged immune function and prevent the recurrence and metastasis.
In conclusion, this is the first demonstration of NK cells adjuvant therapy in combination with surgical treatment and chemotherapy on in patient with advanced gastric signet-ring cell carcinoma. The treatment decisions were fully compliant with the patient’ choices, better reflecting practical clinical situations. NK cells infusion combined with surgical and chemotherapy was well tolerated and showed great potential for the prevention of gastric signet-ring cell carcinoma recurrence and prolonging of survival.